rs2069442

Positions:

• chr7-151058118-G-C

Variant summary

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

The ENST00000483786.5(SLC4A2):​c.-64+837G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 555,224 control chromosomes in the GnomAD database, including 24,798 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 0.32 (8183 hom., cov: 34)
  • Exomes 𝑓: 0.28 (16615 hom.)
• Consequence: SLC4A2 ENST00000483786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000483786.5	c.-64+837G>C		intron_variant		4		ENSP00000417808

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48668 AN: 152120 Hom.: 8170 Cov.: 34

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.281 AC: 113309 AN: 402988 Hom.: 16615 Cov.: 0 AF XY: 0.280 AC XY: 59143 AN XY: 211594

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.320 AC: 48708 AN: 152236 Hom.: 8183 Cov.: 34 AF XY: 0.323 AC XY: 24045 AN XY: 74432

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.309

Alfa AF: 0.308 Hom.: 935

Bravo AF: 0.341

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2069442; hg19: chr7-150755205; COSMIC: COSV52531161; COSMIC: COSV52531161;