Genetic Variant SLC26A4:c.-3-195C>T (chr7-107661444-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000441.2(SLC26A4):c.-3-195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 646,704 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 15 hom. )

Consequence

SLC26A4
NM_000441.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.250

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 7-107661444-C-T is Benign according to our data. Variant chr7-107661444-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2 link	c.-3-195C>T		intron_variant	Intron 1 of 20	ENST00000644269.2	NP_000432.1	O43511-1
SLC26A4-AS1	NR_028137.1 link	n.197+158G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2 link	c.-3-195C>T		intron_variant	Intron 1 of 20		NM_000441.2	ENSP00000494017.1		O43511-1

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

648

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00525

AC:

2594

AN:

494348

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

1308

AN XY:

259964

show subpopulations

African (AFR)

AF:

0.000503

AC:

AN:

13930

American (AMR)

AF:

0.00107

AC:

AN:

25348

Ashkenazi Jewish (ASJ)

AF:

0.000733

AC:

AN:

14998

East Asian (EAS)

AF:

0.0000319

AC:

AN:

31300

South Asian (SAS)

AF:

0.00425

AC:

210

AN:

49456

European-Finnish (FIN)

AF:

0.0248

AC:

750

AN:

30254

Middle Eastern (MID)

AF:

0.00190

AC:

AN:

2102

European-Non Finnish (NFE)

AF:

0.00495

AC:

1481

AN:

299326

Other (OTH)

AF:

0.00373

AC:

103

AN:

27634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

146

292

438

584

730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00425

AC:

648

AN:

152356

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

362

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000529

AC:

AN:

41586

American (AMR)

AF:

0.00118

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00269

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0238

AC:

253

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00497

AC:

338

AN:

68032

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00261

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 22, 2018

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.1

(source)

DANN

Benign

0.75

PhyloP100

-0.25

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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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7-107661444-C-T

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