7-151069712-A-G

Variant names:

• chr7-151069712-A-G
• rs2303933
• NM_003040.4:c.1148-235A>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.1148-235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,668 control chromosomes in the GnomAD database, including 27,208 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 0.60 (27208 hom., cov: 29)
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 14 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 = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	NM_003040.4	MANE Select	c.1148-235A>G		intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.1148-235A>G		intron	N/A	NP_001186621.1
	SLC4A2	NM_001199693.1		c.1121-235A>G		intron	N/A	NP_001186622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.1148-235A>G		intron	N/A	ENSP00000405600.2
	SLC4A2	ENST00000485713.6	TSL:1	c.1148-235A>G		intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.1106-235A>G		intron	N/A	ENSP00000419164.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90324 AN: 151550 Hom.: 27183 Cov.: 29

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.596 AC: 90395 AN: 151668 Hom.: 27208 Cov.: 29 AF XY: 0.604 AC XY: 44732 AN XY: 74116

African (AFR) AF: 0.534 AC: 22096 AN: 41346

American (AMR) AF: 0.700 AC: 10674 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2399 AN: 3464

East Asian (EAS) AF: 0.725 AC: 3698 AN: 5104

South Asian (SAS) AF: 0.514 AC: 2459 AN: 4784

European-Finnish (FIN) AF: 0.700 AC: 7366 AN: 10530

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39543 AN: 67888

Other (OTH) AF: 0.612 AC: 1292 AN: 2110

Alfa AF: 0.588 Hom.: 55539

Bravo AF: 0.599

Asia WGS AF: 0.609 AC: 2118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.16
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: rs2303933; hg19: chr7-150766799;