Genetic Variant SLC26A4:c.-3-109dupG (chr7-107661524-A-AG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000441.2(SLC26A4):c.-3-109dupG 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.397

Publications

0 publications found

Variant links:

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 links:

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

SLC26A4-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2 link	c.-3-109dupG		intron_variant	Intron 1 of 20	ENST00000644269.2	NP_000432.1	O43511-1
SLC26A4-AS1	NR_028137.1 link	n.197+77dupC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2 link	c.-3-109dupG		intron_variant	Intron 1 of 20		NM_000441.2	ENSP00000494017.1		O43511-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2281

AN:

152170

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0167

AC XY:

8641

AN XY:

518600

show subpopulations

African (AFR)

AF:

0.00295

AC:

AN:

24786

American (AMR)

AF:

0.0102

AC:

355

AN:

34866

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

537

AN:

22252

East Asian (EAS)

AF:

0.0000294

AC:

AN:

33980

South Asian (SAS)

AF:

0.00332

AC:

232

AN:

69784

European-Finnish (FIN)

AF:

0.0201

AC:

671

AN:

33432

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

3576

European-Non Finnish (NFE)

AF:

0.0199

AC:

15102

AN:

757036

Other (OTH)

AF:

0.0139

AC:

633

AN:

45642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

921

1842

2764

3685

4606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0150

AC:

2281

AN:

152288

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1095

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00399

AC:

166

AN:

41572

American (AMR)

AF:

0.0135

AC:

207

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0213

AC:

226

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0226

AC:

1534

AN:

68008

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0131

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 22, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism

(source)

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

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7-107661524-A-AG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over