Variant 4-986676-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000398520.6(SLC26A1):c.576+4452T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 425,402 control chromosomes in the GnomAD database, including 46,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16161 hom., cov: 32)

Exomes 𝑓: 0.46 ( 30064 hom. )

Consequence

SLC26A1
ENST00000398520.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.697

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 4-986676-A-G is Benign according to our data. Variant chr4-986676-A-G is described in ClinVar as [Benign]. Clinvar id is 1271915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A1	NM_134425.4 linkuse as main transcript	c.576+4452T>C		intron_variant
SLC26A1	XR_007096347.1 linkuse as main transcript	n.4160+130T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	UniProt
SLC26A1	ENST00000398520.6 linkuse as main transcript	c.576+4452T>C	intron_variant	1	Q9H2B4-2
DGKQ	ENST00000510286.1 linkuse as main transcript	c.46+130T>C	intron_variant	3
SLC26A1	ENST00000622731.4 linkuse as main transcript	c.576+4452T>C	intron_variant	5	Q9H2B4-2

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69699

AN:

151904

Hom.:

16149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.453

GnomAD4 exome

AF:

0.463

AC:

126648

AN:

273380

Hom.:

30064

AF XY:

0.461

AC XY:

70542

AN XY:

153140

show subpopulations

Gnomad4 AFR exome

AF:

0.452

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.359

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.449

GnomAD4 genome

AF:

0.459

AC:

69753

AN:

152022

Hom.:

16161

Cov.:

AF XY:

0.462

AC XY:

34365

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.462

Gnomad4 AMR

AF:

0.522

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.477

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.455

Alfa

AF:

0.450

Hom.:

2447

Bravo

AF:

0.465

Asia WGS

AF:

0.379

AC:

1318

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.3

DANN

Benign

0.20

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