rs11765015

Variant names:

• chr7-151073745-G-A
• rs11765015
• NM_003040.4:c.2536-294G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.2536-294G>A		intron_variant	Intron 16 of 22	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.2536-294G>A		intron_variant	Intron 16 of 22		NP_001186621.1
SLC4A2	NM_001199693.1	c.2509-294G>A		intron_variant	Intron 15 of 21		NP_001186622.1
SLC4A2	NM_001199694.2	c.2494-294G>A		intron_variant	Intron 15 of 21		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.2536-294G>A		intron_variant	Intron 16 of 22	1	NM_003040.4	ENSP00000405600.2

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

African (AFR) AF: 0.202 AC: 8387 AN: 41490

American (AMR) AF: 0.396 AC: 6045 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2036 AN: 5150

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4826

European-Finnish (FIN) AF: 0.283 AC: 2988 AN: 10566

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17669 AN: 67974

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.272 Hom.: 7743

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
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11765015; hg19: chr7-150770832;