4-979583-G-A

Variant summary

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

The ENST00000398520.6(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 ENST00000398520.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.316

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=-0.9).
• 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_single_submitter, 1 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/exons	MANE	UniProt
SLC26A1	NM_134425.4	c.577-79C>T		intron_variant
SLC26A1	XR_007096347.1	n.4161-79C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A1	ENST00000398520.6	c.577-79C>T		intron_variant		1
DGKQ	ENST00000510286.1	c.46+7223C>T		intron_variant		3
SLC26A1	ENST00000622731.4	c.577-79C>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.0979

Gnomad4 AMR exome AF: 0.00535

Gnomad4 ASJ exome AF: 0.00127

Gnomad4 EAS exome AF: 0.0000515

Gnomad4 SAS exome AF: 0.000407

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.000252

Gnomad4 OTH exome AF: 0.00698

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

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0116 Hom.: 13

Bravo AF: 0.0304

Asia WGS AF: 0.00606 AC: 21 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

Jul 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10008164; hg19: chr4-973371;