4-986676-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.697

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.576+4452T>C		intron_variant
SLC26A1	XR_007096347.1	n.4160+130T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A1	ENST00000398520.6	c.576+4452T>C		intron_variant		1
DGKQ	ENST00000510286.1	c.46+130T>C		intron_variant		3
SLC26A1	ENST00000622731.4	c.576+4452T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69699 AN: 151904 Hom.: 16149 Cov.: 32

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

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.: 32 AF XY: 0.462 AC XY: 34365 AN XY: 74332

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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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

Other links and lift over

dbSNP: rs4690220; hg19: chr4-980464; COSMIC: COSV56103740; COSMIC: COSV56103740;