rs2072064

Variant names:

• chr7-107694068-T-A
• rs2072064
• NM_000441.2:c.1264-335T>A

Variant summary

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

The NM_000441.2(SLC26A4):​c.1264-335T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,152 control chromosomes in the GnomAD database, including 4,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4520 hom., cov: 32)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.281
• Publications: 8 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=-0.75).
• BP6: Variant 7-107694068-T-A is Benign according to our data. Variant chr7-107694068-T-A is described in ClinVar as Benign. ClinVar VariationId is 1290048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.1264-335T>A		intron_variant	Intron 10 of 20	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.1264-335T>A		intron_variant	Intron 10 of 20		NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33014 AN: 152032 Hom.: 4515 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.217 AC: 33035 AN: 152152 Hom.: 4520 Cov.: 32 AF XY: 0.227 AC XY: 16901 AN XY: 74360

African (AFR) AF: 0.0496 AC: 2060 AN: 41552

American (AMR) AF: 0.311 AC: 4745 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1844 AN: 5162

South Asian (SAS) AF: 0.437 AC: 2104 AN: 4820

European-Finnish (FIN) AF: 0.324 AC: 3423 AN: 10574

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17306 AN: 67990

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.239 Hom.: 607

Bravo AF: 0.206

Asia WGS AF: 0.394 AC: 1364 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.4
DANN	Benign	0.83
PhyloP100		-0.28
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: rs2072064; hg19: chr7-107334513;