rs6856425

chr4-983130-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398520.6(SLC26A1):c.577-3626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,324 control chromosomes in the GnomAD database, including 742 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (742 hom., cov: 33)
• Consequence: SLC26A1 ENST00000398520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A1	NM_134425.4	c.577-3626A>G		intron_variant
SLC26A1	XR_007096347.1	n.4161-3626A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A1	ENST00000398520.6	c.577-3626A>G		intron_variant		1
DGKQ	ENST00000510286.1	c.46+3676A>G		intron_variant		3
SLC26A1	ENST00000622731.4	c.577-3626A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11258 AN: 152206 Hom.: 740 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.0310

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0741 AC: 11282 AN: 152324 Hom.: 742 Cov.: 33 AF XY: 0.0728 AC XY: 5421 AN XY: 74502

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0394 Hom.: 107

Bravo AF: 0.0783

Asia WGS AF: 0.0790 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.052
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6856425; hg19: chr4-976918;