NM_003040.4:c.579-733G>A

Variant names:

• chr7-151065784-G-A
• rs3793336
• NM_003040.4:c.579-733G>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.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
• Publications: 10 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=-0.89).
• 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 rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.579-733G>A		intron_variant	Intron 5 of 22	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.579-733G>A		intron_variant	Intron 5 of 22		NP_001186621.1
SLC4A2	NM_001199693.1	c.552-733G>A		intron_variant	Intron 4 of 21		NP_001186622.1
SLC4A2	NM_001199694.2	c.537-733G>A		intron_variant	Intron 4 of 21		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.579-733G>A		intron_variant	Intron 5 of 22	1	NM_003040.4	ENSP00000405600.2

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

African (AFR) AF: 0.902 AC: 37409 AN: 41470

American (AMR) AF: 0.892 AC: 13648 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3099 AN: 3464

East Asian (EAS) AF: 0.940 AC: 4846 AN: 5158

South Asian (SAS) AF: 0.825 AC: 3960 AN: 4800

European-Finnish (FIN) AF: 0.863 AC: 9123 AN: 10576

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56878 AN: 67970

Other (OTH) AF: 0.870 AC: 1836 AN: 2110

Alfa AF: 0.846 Hom.: 87772

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
PhyloP100		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3793336; hg19: chr7-150762871;