rs4690220

Variant names:

• chr4-986676-A-G
• rs4690220
• ENST00000398520.6:c.576+4452T>C

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.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 NM_134425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.697
• Publications: 29 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=-0.99).
• 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 rank	MANE	Protein	UniProt
SLC26A1	NM_134425.4	c.576+4452T>C		intron_variant	Intron 2 of 2		NP_602297.1
SLC26A1	XR_007096347.1	n.4160+130T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A1	ENST00000398520.6	c.576+4452T>C		intron_variant	Intron 2 of 2	1		ENSP00000381532.2
SLC26A1	ENST00000622731.4	c.576+4452T>C		intron_variant	Intron 3 of 3	5		ENSP00000483506.1
DGKQ	ENST00000510286.1	c.46+130T>C		intron_variant	Intron 1 of 4	3		ENSP00000427268.1

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

African (AFR) AF: 0.452 AC: 3531 AN: 7804

American (AMR) AF: 0.579 AC: 14530 AN: 25078

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 3410 AN: 9788

East Asian (EAS) AF: 0.359 AC: 3042 AN: 8464

South Asian (SAS) AF: 0.472 AC: 26849 AN: 56844

European-Finnish (FIN) AF: 0.461 AC: 5434 AN: 11776

Middle Eastern (MID) AF: 0.418 AC: 1002 AN: 2398

European-Non Finnish (NFE) AF: 0.456 AC: 63133 AN: 138508

Other (OTH) AF: 0.449 AC: 5717 AN: 12720

GnomAD4 genome AF: 0.459 AC: 69753 AN: 152022 Hom.: 16161 Cov.: 32 AF XY: 0.462 AC XY: 34365 AN XY: 74332

African (AFR) AF: 0.462 AC: 19138 AN: 41448

American (AMR) AF: 0.522 AC: 7983 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1894 AN: 5170

South Asian (SAS) AF: 0.477 AC: 2305 AN: 4830

European-Finnish (FIN) AF: 0.474 AC: 5019 AN: 10578

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30922 AN: 67928

Other (OTH) AF: 0.455 AC: 958 AN: 2106

Alfa AF: 0.459 Hom.: 4376

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

Submissions by phenotype

not provided Benign:2

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.20
PhyloP100		-0.70
PromoterAI		0.010	Neutral
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: rs4690220; hg19: chr4-980464; COSMIC: COSV56103740; COSMIC: COSV56103740;