chr4-979248-C-T

Variant names:

• chr4-979248-C-T
• rs4583705
• ENST00000398520.6:c.*158G>A

Variant summary

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

The XR_007096347.1(SLC26A1):​n.4417G>A variant causes a non coding transcript exon 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 XR_007096347.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.274
• Publications: 11 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=-0.84).
• 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLC26A1	XR_007096347.1	n.4417G>A		non_coding_transcript_exon_variant	Exon 3 of 3
SLC26A1	NM_134425.4	c.*158G>A		3_prime_UTR_variant	Exon 3 of 3		NP_602297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A1	ENST00000398520.6	c.*158G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000381532.2
DGKQ	ENST00000510286.1	c.46+7558G>A		intron_variant	Intron 1 of 4	3		ENSP00000427268.1
SLC26A1	ENST00000622731.4	c.*158G>A		downstream_gene_variant		5		ENSP00000483506.1

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

African (AFR) AF: 0.0316 AC: 386 AN: 12232

American (AMR) AF: 0.0529 AC: 978 AN: 18502

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 2947 AN: 13638

East Asian (EAS) AF: 0.129 AC: 3881 AN: 30104

South Asian (SAS) AF: 0.214 AC: 9080 AN: 42414

European-Finnish (FIN) AF: 0.168 AC: 5255 AN: 31236

Middle Eastern (MID) AF: 0.0987 AC: 209 AN: 2118

European-Non Finnish (NFE) AF: 0.110 AC: 28733 AN: 261152

Other (OTH) AF: 0.115 AC: 2904 AN: 25316

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

African (AFR) AF: 0.0296 AC: 1231 AN: 41556

American (AMR) AF: 0.0680 AC: 1041 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.120 AC: 624 AN: 5186

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1802 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7605 AN: 68016

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.101 Hom.: 1241

Bravo AF: 0.0794

Asia WGS AF: 0.181 AC: 628 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 09, 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	-0.84
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.27
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: rs4583705; hg19: chr4-973036; COSMIC: COSV68310790; COSMIC: COSV68310790;