chr7-107661656-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_000441.2(SLC26A4):​c.15C>A​(p.Gly5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,567,138 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0062 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00069 ( 7 hom. )

Consequence

SLC26A4
NM_000441.2 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:10

Conservation

PhyloP100: 0.365
Variant links:
Genes affected
SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]
SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 7-107661656-C-A is Benign according to our data. Variant chr7-107661656-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43515.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2, Benign=6}. Variant chr7-107661656-C-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.365 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00617 (940/152384) while in subpopulation AFR AF= 0.0213 (886/41596). AF 95% confidence interval is 0.0201. There are 8 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC26A4NM_000441.2 linkuse as main transcriptc.15C>A p.Gly5= synonymous_variant 2/21 ENST00000644269.2
SLC26A4-AS1NR_028137.1 linkuse as main transcriptn.143G>T non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC26A4ENST00000644269.2 linkuse as main transcriptc.15C>A p.Gly5= synonymous_variant 2/21 NM_000441.2 P1O43511-1
SLC26A4-AS1ENST00000668981.1 linkuse as main transcriptn.203G>T non_coding_transcript_exon_variant 1/2

Frequencies

GnomAD3 genomes
AF:
0.00617
AC:
939
AN:
152266
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0213
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000413
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00145
AC:
256
AN:
176868
Hom.:
5
AF XY:
0.00108
AC XY:
105
AN XY:
96938
show subpopulations
Gnomad AFR exome
AF:
0.0229
Gnomad AMR exome
AF:
0.000968
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000400
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000900
Gnomad OTH exome
AF:
0.000833
GnomAD4 exome
AF:
0.000688
AC:
973
AN:
1414754
Hom.:
7
Cov.:
30
AF XY:
0.000619
AC XY:
434
AN XY:
700636
show subpopulations
Gnomad4 AFR exome
AF:
0.0239
Gnomad4 AMR exome
AF:
0.00113
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000246
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000494
Gnomad4 OTH exome
AF:
0.00134
GnomAD4 genome
AF:
0.00617
AC:
940
AN:
152384
Hom.:
8
Cov.:
32
AF XY:
0.00627
AC XY:
467
AN XY:
74532
show subpopulations
Gnomad4 AFR
AF:
0.0213
Gnomad4 AMR
AF:
0.00202
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.000475
Hom.:
0
Bravo
AF:
0.00676
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:10
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Pendred syndrome Uncertain:1Benign:3
Likely benign, criteria provided, single submitterclinical testingCounsylMay 29, 2018- -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Benign, no assertion criteria providedclinical testingNatera, Inc.Oct 18, 2019- -
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Benign:4
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsFeb 22, 2019- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024SLC26A4: BP4, BP7, BS1, BS2; SLC26A4-AS1: BS1, BS2 -
Benign, criteria provided, single submitterclinical testingGeneDxDec 23, 2019This variant is associated with the following publications: (PMID: 29739340, 23280318) -
Autosomal recessive nonsyndromic hearing loss 4 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineAug 24, 2012Gly5Gly in exon 2 of SLC26A4: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 1.4% (54/3922) of African American chromosomes from a broad population by the NHLBI Exome sequencing proje ct (http://evs.gs.washington.edu/EVS/). -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
13
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7811324; hg19: chr7-107302101; API