7-107683668-G-T

Variant names:

• chr7-107683668-G-T
• rs2395911
• NM_000441.2:c.1001+131G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000644269.2(SLC26A4):​c.1001+131G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 753,910 control chromosomes in the GnomAD database, including 201,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (43558 hom., cov: 32)
  • Exomes 𝑓: 0.72 (157835 hom.)
• Consequence: SLC26A4 ENST00000644269.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230
• Publications: 11 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-107683668-G-T is Benign according to our data. Variant chr7-107683668-G-T is described in ClinVar as Benign. ClinVar VariationId is 1236994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644269.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	NM_000441.2	MANE Select	c.1001+131G>T		intron	N/A	NP_000432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.1001+131G>T		intron	N/A	ENSP00000494017.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114454 AN: 151904 Hom.: 43545 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.721 AC: 434121 AN: 601888 Hom.: 157835 AF XY: 0.715 AC XY: 227094 AN XY: 317426

African (AFR) AF: 0.858 AC: 12953 AN: 15100

American (AMR) AF: 0.641 AC: 15466 AN: 24146

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 12441 AN: 16964

East Asian (EAS) AF: 0.630 AC: 19993 AN: 31714

South Asian (SAS) AF: 0.590 AC: 31508 AN: 53414

European-Finnish (FIN) AF: 0.689 AC: 24711 AN: 35874

Middle Eastern (MID) AF: 0.719 AC: 1737 AN: 2416

European-Non Finnish (NFE) AF: 0.748 AC: 292419 AN: 391090

Other (OTH) AF: 0.734 AC: 22893 AN: 31170

GnomAD4 genome AF: 0.753 AC: 114516 AN: 152022 Hom.: 43558 Cov.: 32 AF XY: 0.743 AC XY: 55211 AN XY: 74280

African (AFR) AF: 0.855 AC: 35488 AN: 41486

American (AMR) AF: 0.665 AC: 10143 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2544 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3292 AN: 5168

South Asian (SAS) AF: 0.580 AC: 2798 AN: 4820

European-Finnish (FIN) AF: 0.685 AC: 7214 AN: 10534

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50547 AN: 67972

Other (OTH) AF: 0.748 AC: 1575 AN: 2106

Alfa AF: 0.736 Hom.: 47976

Bravo AF: 0.760

Asia WGS AF: 0.587 AC: 2046 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.56
PhyloP100		0.23
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: rs2395911; hg19: chr7-107324113;