rs11765015

Positions:

• chr7-151073745-G-A

Variant summary

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

The NM_003040.4(SLC4A2):​c.2536-294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,050 control chromosomes in the GnomAD database, including 5,766 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 0.27 (5766 hom., cov: 32)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.2536-294G>A		intron_variant		ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.2536-294G>A		intron_variant			NP_001186621.1
SLC4A2	NM_001199693.1	c.2509-294G>A		intron_variant			NP_001186622.1
SLC4A2	NM_001199694.2	c.2494-294G>A		intron_variant			NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.2536-294G>A		intron_variant		1	NM_003040.4	ENSP00000405600	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40549 AN: 151932 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40579 AN: 152050 Hom.: 5766 Cov.: 32 AF XY: 0.272 AC XY: 20199 AN XY: 74324

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.279

Alfa AF: 0.271 Hom.: 5819

Bravo AF: 0.280

Asia WGS AF: 0.330 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs11765015; hg19: chr7-150770832;