7-107661378-C-T

Position:

• chr7-107661378-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000441.2(SLC26A4):​c.-3-261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 579,984 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (46 hom., cov: 32)
  • Exomes 𝑓: 0.027 (231 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.423

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-107661378-C-T is Benign according to our data. Variant chr7-107661378-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2854/152350) while in subpopulation NFE AF= 0.027 (1839/68018). AF 95% confidence interval is 0.026. There are 46 homozygotes in gnomad4. There are 1328 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.-3-261C>T		intron_variant		ENST00000644269.2	NP_000432.1
SLC26A4-AS1	NR_028137.1	n.197+224G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.-3-261C>T		intron_variant			NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2856 AN: 152232 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.00649

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0266 AC: 11388 AN: 427634 Hom.: 231 Cov.: 2 AF XY: 0.0278 AC XY: 6263 AN XY: 225504

Gnomad4 AFR exome AF: 0.00461

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.00997

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0286

GnomAD4 genome AF: 0.0187 AC: 2854 AN: 152350 Hom.: 46 Cov.: 32 AF XY: 0.0178 AC XY: 1328 AN XY: 74496

Gnomad4 AFR AF: 0.00462

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.00649

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0231 Hom.: 9

Bravo AF: 0.0194

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs55753070; hg19: chr7-107301823;