rs3793336

chr7-151065784-G-Achr7-151065784-G-Cchr7-151065784-G-T

Variant summary

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

The NM_003040.4(SLC4A2):c.579-733G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,044 control chromosomes in the GnomAD database, including 57,227 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 0.87 (57227 hom., cov: 31)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.579-733G>A		intron_variant		ENST00000413384.7
SLC4A2	NM_001199692.3	c.579-733G>A		intron_variant
SLC4A2	NM_001199693.1	c.552-733G>A		intron_variant
SLC4A2	NM_001199694.2	c.537-733G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.579-733G>A		intron_variant		1	NM_003040.4	P1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131729 AN: 151926 Hom.: 57176 Cov.: 31

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.847

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.867 AC: 131837 AN: 152044 Hom.: 57227 Cov.: 31 AF XY: 0.867 AC XY: 64434 AN XY: 74312

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.870

Alfa AF: 0.841 Hom.: 63106

Bravo AF: 0.873

Asia WGS AF: 0.882 AC: 3069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.73
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3793336; hg19: chr7-150762871;