rs2303930

Variant names:

• chr7-151064461-A-G
• rs2303930
• NM_003040.4:c.218-65A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003040.4(SLC4A2):​c.218-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,563,010 control chromosomes in the GnomAD database, including 98,054 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 0.34 (8459 hom., cov: 25)
  • Exomes 𝑓: 0.35 (89595 hom.)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.218-65A>G		intron_variant	Intron 3 of 22	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.218-65A>G		intron_variant	Intron 3 of 22		NP_001186621.1
SLC4A2	NM_001199693.1	c.191-65A>G		intron_variant	Intron 2 of 21		NP_001186622.1
SLC4A2	NM_001199694.2	c.176-65A>G		intron_variant	Intron 2 of 21		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.218-65A>G		intron_variant	Intron 3 of 22	1	NM_003040.4	ENSP00000405600.2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 49076 AN: 145220 Hom.: 8454 Cov.: 25

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.353 AC: 500682 AN: 1417694 Hom.: 89595 Cov.: 34 AF XY: 0.352 AC XY: 246462 AN XY: 699732

African (AFR) AF: 0.260 AC: 8500 AN: 32748

American (AMR) AF: 0.218 AC: 9342 AN: 42824

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 10094 AN: 23790

East Asian (EAS) AF: 0.323 AC: 12650 AN: 39168

South Asian (SAS) AF: 0.298 AC: 24206 AN: 81334

European-Finnish (FIN) AF: 0.423 AC: 21757 AN: 51454

Middle Eastern (MID) AF: 0.369 AC: 1468 AN: 3980

European-Non Finnish (NFE) AF: 0.361 AC: 391767 AN: 1084072

Other (OTH) AF: 0.358 AC: 20898 AN: 58324

GnomAD4 genome AF: 0.338 AC: 49111 AN: 145316 Hom.: 8459 Cov.: 25 AF XY: 0.339 AC XY: 23954 AN XY: 70716

African (AFR) AF: 0.271 AC: 10452 AN: 38574

American (AMR) AF: 0.317 AC: 4626 AN: 14604

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1392 AN: 3374

East Asian (EAS) AF: 0.321 AC: 1564 AN: 4868

South Asian (SAS) AF: 0.287 AC: 1318 AN: 4588

European-Finnish (FIN) AF: 0.434 AC: 4261 AN: 9820

Middle Eastern (MID) AF: 0.378 AC: 109 AN: 288

European-Non Finnish (NFE) AF: 0.368 AC: 24421 AN: 66296

Other (OTH) AF: 0.352 AC: 713 AN: 2024

Alfa AF: 0.343 Hom.: 1112

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.37
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2303930; hg19: chr7-150761548;