Variant 4-986813-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000398520.6(SLC26A1):c.576+4315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 611,646 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

SLC26A1
ENST00000398520.6 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.505

Variant links:

Genes affected

SLC26A1 (HGNC:10993): (solute carrier family 26 member 1) This gene is a member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures, but have markedly different tissue expression patterns. This gene is primarily expressed in the liver, pancreas, and brain. Three splice variants that encode different isoforms have been identified. [provided by RefSeq, Jul 2008]

SLC26A1 links:

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

DGKQ links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037944317).

BP6

Variant 4-986813-C-G is Benign according to our data. Variant chr4-986813-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1208686.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A1	NM_134425.4 linkuse as main transcript	c.576+4315G>C		intron_variant			NP_602297.1
SLC26A1	XR_007096347.1 linkuse as main transcript	n.4153G>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
SLC26A1	ENST00000398520.6 linkuse as main transcript	c.576+4315G>C		intron_variant		1	ENSP00000381532	Q9H2B4-2
DGKQ	ENST00000510286.1 linkuse as main transcript	c.39G>C	p.Leu13Phe	missense_variant	1/5	3	ENSP00000427268
SLC26A1	ENST00000622731.4 linkuse as main transcript	c.576+4315G>C		intron_variant		5	ENSP00000483506	Q9H2B4-2

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

478

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000771

AC:

AN:

128400

Hom.:

AF XY:

0.000597

AC XY:

AN XY:

70320

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.000534

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000250

GnomAD4 exome

AF:

0.000433

AC:

199

AN:

459286

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

251914

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.000820

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000386

Gnomad4 OTH exome

AF:

0.000777

GnomAD4 genome

AF:

0.00315

AC:

480

AN:

152360

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000685

Hom.:

Bravo

AF:

0.00400

ExAC

AF:

0.000378

AC:

Asia WGS

AF:

0.000866

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.7

DANN

Benign

0.48

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PROVEAN

Benign

0.17

REVEL

Benign

0.073

Sift

Pathogenic

0.0

MutPred

0.29

Loss of helix (P = 0.0076);

MVP

0.12

ClinPred

0.023

GERP RS

-0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over