7-107666761-C-T

Variant names:

• chr7-107666761-C-T
• rs2701688
• NM_000441.2:c.304+3326C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000441.2(SLC26A4):​c.304+3326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,904 control chromosomes in the GnomAD database, including 6,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6543 hom., cov: 31)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.304+3326C>T		intron_variant	Intron 3 of 20	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.304+3326C>T		intron_variant	Intron 3 of 20		NM_000441.2	ENSP00000494017.1
SLC26A4	ENST00000440056.1	c.304+3326C>T		intron_variant	Intron 3 of 3	4		ENSP00000394760.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43777 AN: 151788 Hom.: 6542 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.288 AC: 43807 AN: 151904 Hom.: 6543 Cov.: 31 AF XY: 0.288 AC XY: 21400 AN XY: 74204

African (AFR) AF: 0.262 AC: 10848 AN: 41432

American (AMR) AF: 0.246 AC: 3747 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3470

East Asian (EAS) AF: 0.241 AC: 1241 AN: 5150

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3344 AN: 10534

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21477 AN: 67932

Other (OTH) AF: 0.270 AC: 569 AN: 2106

Alfa AF: 0.299 Hom.: 12361

Bravo AF: 0.278

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.19
PhyloP100		-0.38
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: rs2701688; hg19: chr7-107307206;