7-107661524-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000441.2(SLC26A4):c.-3-109dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,177,642 control chromosomes in the GnomAD database, including 196 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (26 hom., cov: 32)
  • Exomes 𝑓: 0.017 (170 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.397

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-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-107661524-A-AG is Benign according to our data. Variant chr7-107661524-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 1209241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2281/152288) while in subpopulation NFE AF= 0.0226 (1534/68008). AF 95% confidence interval is 0.0216. There are 26 homozygotes in gnomad4. There are 1095 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.-3-109dup		intron_variant		ENST00000644269.2
SLC26A4-AS1	NR_028137.1	n.197+77_197+78insC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.-3-109dup		intron_variant			NM_000441.2	P1
SLC26A4-AS1	ENST00000668981.1	n.257+77_257+78insC		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2281 AN: 152170 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00400

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0172 AC: 17609 AN: 1025354 Hom.: 170 Cov.: 14 AF XY: 0.0167 AC XY: 8641 AN XY: 518600

Gnomad4 AFR exome AF: 0.00295

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.0241

Gnomad4 EAS exome AF: 0.0000294

Gnomad4 SAS exome AF: 0.00332

Gnomad4 FIN exome AF: 0.0201

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0150 AC: 2281 AN: 152288 Hom.: 26 Cov.: 32 AF XY: 0.0147 AC XY: 1095 AN XY: 74468

Gnomad4 AFR AF: 0.00399

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0170

Bravo AF: 0.0131

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 22, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs200483647; hg19: chr7-107301969;