chr7-107663183-C-T

Position:

• chr7-107663183-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000441.2(SLC26A4):​c.165-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,194,196 control chromosomes in the GnomAD database, including 313,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37474 hom., cov: 32)
  • Exomes 𝑓: 0.72 (275872 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-107663183-C-T is Benign according to our data. Variant chr7-107663183-C-T is described in ClinVar as [Benign]. Clinvar id is 1228891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.165-113C>T		intron_variant		ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.165-113C>T		intron_variant			NM_000441.2	ENSP00000494017.1
SLC26A4	ENST00000440056.1	c.165-113C>T		intron_variant		4		ENSP00000394760.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106137 AN: 151460 Hom.: 37437 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.724 AC: 754673 AN: 1042618 Hom.: 275872 AF XY: 0.727 AC XY: 390536 AN XY: 537498

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.701 AC: 106233 AN: 151578 Hom.: 37474 Cov.: 32 AF XY: 0.701 AC XY: 51899 AN XY: 74028

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.716

Alfa AF: 0.721 Hom.: 43975

Bravo AF: 0.688

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.24

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: rs2248465; hg19: chr7-107303628; COSMIC: COSV55919158; COSMIC: COSV55919158;