4-979248-C-T

Variant summary

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

The ENST00000398520.6(SLC26A1):c.*158G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 588,954 control chromosomes in the GnomAD database, including 4,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (942 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3960 hom.)
• Consequence: SLC26A1 ENST00000398520.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.274

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=-0.84).
• BP6: Variant 4-979248-C-T is Benign according to our data. Variant chr4-979248-C-T is described in ClinVar as [Benign]. Clinvar id is 1269605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A1	NM_134425.4	c.*158G>A		3_prime_UTR_variant	3/3
SLC26A1	XR_007096347.1	n.4417G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A1	ENST00000398520.6	c.*158G>A		3_prime_UTR_variant	3/3	1
DGKQ	ENST00000510286.1	c.46+7558G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14419 AN: 152122 Hom.: 942 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0994

GnomAD4 exome AF: 0.125 AC: 54373 AN: 436712 Hom.: 3960 Cov.: 3 AF XY: 0.130 AC XY: 29852 AN XY: 229790

Gnomad4 AFR exome AF: 0.0316

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0948 AC: 14425 AN: 152242 Hom.: 942 Cov.: 32 AF XY: 0.0986 AC XY: 7341 AN XY: 74428

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.105 Hom.: 880

Bravo AF: 0.0794

Asia WGS AF: 0.181 AC: 628 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 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4583705; hg19: chr4-973036; COSMIC: COSV68310790; COSMIC: COSV68310790;