4-986922-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000398520.6(SLC26A1):c.576+4206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 718,066 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (9 hom.)
• Consequence: SLC26A1 ENST00000398520.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214

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=-0.8).
• BP6: Variant 4-986922-C-T is Benign according to our data. Variant chr4-986922-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2023/152320) while in subpopulation AFR AF= 0.0454 (1886/41576). AF 95% confidence interval is 0.0437. There are 38 homozygotes in gnomad4. There are 959 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A1	NM_134425.4	c.576+4206G>A		intron_variant
SLC26A1	XR_007096347.1	n.4044G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A1	ENST00000398520.6	c.576+4206G>A		intron_variant		1
SLC26A1	ENST00000622731.4	c.576+4206G>A		intron_variant		5
DGKQ	ENST00000510286.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2024 AN: 152204 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00109 AC: 617 AN: 565746 Hom.: 9 Cov.: 7 AF XY: 0.000857 AC XY: 260 AN XY: 303232

Gnomad4 AFR exome AF: 0.0311

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000360

Gnomad4 SAS exome AF: 0.0000797

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000434

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.0133 AC: 2023 AN: 152320 Hom.: 38 Cov.: 33 AF XY: 0.0129 AC XY: 959 AN XY: 74478

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.00751

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0112 Hom.: 5

Bravo AF: 0.0145

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.0
Dann	Benign	0.82
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		3.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116840205; hg19: chr4-980710;