rs2303930

Positions:

• chr7-151064461-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• 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/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.218-65A>G		intron_variant		ENST00000413384.7
SLC4A2	NM_001199692.3	c.218-65A>G		intron_variant
SLC4A2	NM_001199693.1	c.191-65A>G		intron_variant
SLC4A2	NM_001199694.2	c.176-65A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.218-65A>G		intron_variant		1	NM_003040.4	P1

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

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.358

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.352

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

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: rs2303930; hg19: chr7-150761548;