rs2188561

Positions:

• chr7-107695613-C-A
• chr7-107695613-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000441.2(SLC26A4):​c.1438-320C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,992 control chromosomes in the GnomAD database, including 3,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3602 hom., cov: 32)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.24

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 7-107695613-C-A is Benign according to our data. Variant chr7-107695613-C-A is described in ClinVar as [Benign]. Clinvar id is 1225871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.1438-320C>A		intron_variant		ENST00000644269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.1438-320C>A		intron_variant			NM_000441.2	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29256 AN: 151874 Hom.: 3600 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29268 AN: 151992 Hom.: 3602 Cov.: 32 AF XY: 0.204 AC XY: 15131 AN XY: 74280

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.202

Alfa AF: 0.0783 Hom.: 101

Bravo AF: 0.183

Asia WGS AF: 0.374 AC: 1296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.084
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs2188561; hg19: chr7-107336058;