rs2248465

Variant names:

• chr7-107663183-C-T
• rs2248465
• NM_000441.2:c.165-113C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-107663183-C-T
• chr7-107663183-C-A
• chr7-107663183-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Pendred syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• athyreosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid hypoplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	NM_000441.2	MANE Select	c.165-113C>T		intron	N/A	NP_000432.1	O43511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.165-113C>T		intron	N/A	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.165-113C>T		intron	N/A	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.165-113C>T		intron	N/A	ENSP00000558759.1

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

African (AFR) AF: 0.666 AC: 16701 AN: 25082

American (AMR) AF: 0.706 AC: 30654 AN: 43404

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 15032 AN: 23372

East Asian (EAS) AF: 0.432 AC: 16301 AN: 37716

South Asian (SAS) AF: 0.800 AC: 61296 AN: 76654

European-Finnish (FIN) AF: 0.767 AC: 40468 AN: 52756

Middle Eastern (MID) AF: 0.776 AC: 3820 AN: 4920

European-Non Finnish (NFE) AF: 0.734 AC: 537487 AN: 732352

Other (OTH) AF: 0.710 AC: 32914 AN: 46362

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

African (AFR) AF: 0.665 AC: 27502 AN: 41332

American (AMR) AF: 0.707 AC: 10779 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2267 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2318 AN: 5174

South Asian (SAS) AF: 0.794 AC: 3821 AN: 4814

European-Finnish (FIN) AF: 0.763 AC: 7976 AN: 10454

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49223 AN: 67790

Other (OTH) AF: 0.716 AC: 1507 AN: 2104

Alfa AF: 0.720 Hom.: 59153

Bravo AF: 0.688

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.24
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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