chr4-979583-G-A

Variant names:

• chr4-979583-G-A
• rs10008164
• ENST00000398520.6:c.577-79C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_134425.4(SLC26A1):​c.577-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,578,024 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (183 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (173 hom.)
• Consequence: SLC26A1 NM_134425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.316
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-979583-G-A is Benign according to our data. Variant chr4-979583-G-A is described in ClinVar as [Benign]. Clinvar id is 1293883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A1	NM_134425.4	c.577-79C>T		intron_variant	Intron 2 of 2		NP_602297.1
SLC26A1	XR_007096347.1	n.4161-79C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A1	ENST00000398520.6	c.577-79C>T		intron_variant	Intron 2 of 2	1		ENSP00000381532.2
SLC26A1	ENST00000622731.4	c.577-79C>T		intron_variant	Intron 3 of 3	5		ENSP00000483506.1
DGKQ	ENST00000510286.1	c.46+7223C>T		intron_variant	Intron 1 of 4	3		ENSP00000427268.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4052 AN: 152190 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00296 AC: 4213 AN: 1425716 Hom.: 173 AF XY: 0.00260 AC XY: 1839 AN XY: 707524

African (AFR) AF: 0.0979 AC: 3202 AN: 32706

American (AMR) AF: 0.00535 AC: 228 AN: 42652

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 32 AN: 25288

East Asian (EAS) AF: 0.0000515 AC: 2 AN: 38858

South Asian (SAS) AF: 0.000407 AC: 34 AN: 83460

European-Finnish (FIN) AF: 0.000101 AC: 5 AN: 49636

Middle Eastern (MID) AF: 0.00505 AC: 25 AN: 4952

European-Non Finnish (NFE) AF: 0.000252 AC: 274 AN: 1089272

Other (OTH) AF: 0.00698 AC: 411 AN: 58892

GnomAD4 genome AF: 0.0266 AC: 4051 AN: 152308 Hom.: 183 Cov.: 32 AF XY: 0.0258 AC XY: 1922 AN XY: 74488

African (AFR) AF: 0.0918 AC: 3815 AN: 41560

American (AMR) AF: 0.00987 AC: 151 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68016

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.0387 Hom.: 84

Bravo AF: 0.0304

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 14, 2018

GeneDx

Significance: 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	-0.90
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10008164; hg19: chr4-973371;