NM_003040.4:c.2202G>A

Variant names:

• chr7-151071699-G-A
• rs2303937
• NM_003040.4:c.2202G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003040.4(SLC4A2):​c.2202G>A​(p.Thr734Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,608,334 control chromosomes in the GnomAD database, including 168,097 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 0.43 (14512 hom., cov: 31)
  • Exomes 𝑓: 0.46 (153585 hom.)
• Consequence: SLC4A2 NM_003040.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.15
• Publications: 31 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-5.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	NM_003040.4	MANE Select	c.2202G>A	p.Thr734Thr	synonymous	Exon 15 of 23	NP_003031.3
	SLC4A2	NM_001199692.3		c.2202G>A	p.Thr734Thr	synonymous	Exon 15 of 23	NP_001186621.1
	SLC4A2	NM_001199693.1		c.2175G>A	p.Thr725Thr	synonymous	Exon 14 of 22	NP_001186622.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.2202G>A	p.Thr734Thr	synonymous	Exon 15 of 23	ENSP00000405600.2
	SLC4A2	ENST00000485713.6	TSL:1	c.2202G>A	p.Thr734Thr	synonymous	Exon 15 of 23	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.2160G>A	p.Thr720Thr	synonymous	Exon 14 of 22	ENSP00000419164.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65629 AN: 151732 Hom.: 14505 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.433

GnomAD2 exomes AF: 0.482 AC: 119610 AN: 247944 AF XY: 0.480

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.660

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.433

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.456 AC: 664643 AN: 1456486 Hom.: 153585 Cov.: 54 AF XY: 0.458 AC XY: 331791 AN XY: 724030

African (AFR) AF: 0.362 AC: 12071 AN: 33324

American (AMR) AF: 0.650 AC: 28792 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 12028 AN: 25816

East Asian (EAS) AF: 0.428 AC: 16967 AN: 39614

South Asian (SAS) AF: 0.540 AC: 46378 AN: 85940

European-Finnish (FIN) AF: 0.427 AC: 22633 AN: 52952

Middle Eastern (MID) AF: 0.473 AC: 2706 AN: 5722

European-Non Finnish (NFE) AF: 0.447 AC: 495769 AN: 1108684

Other (OTH) AF: 0.454 AC: 27299 AN: 60120

GnomAD4 genome AF: 0.432 AC: 65661 AN: 151848 Hom.: 14512 Cov.: 31 AF XY: 0.435 AC XY: 32261 AN XY: 74190

African (AFR) AF: 0.362 AC: 14967 AN: 41392

American (AMR) AF: 0.523 AC: 7988 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2198 AN: 5140

South Asian (SAS) AF: 0.533 AC: 2562 AN: 4808

European-Finnish (FIN) AF: 0.421 AC: 4448 AN: 10576

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30288 AN: 67876

Other (OTH) AF: 0.438 AC: 923 AN: 2106

Alfa AF: 0.438 Hom.: 27339

Bravo AF: 0.440

Asia WGS AF: 0.494 AC: 1717 AN: 3478

EpiCase AF: 0.436

EpiControl AF: 0.437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.5
DANN	Benign	0.82
PhyloP100		-5.1
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)		0.040		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: rs2303937; hg19: chr7-150768786; COSMIC: COSV52540106; COSMIC: COSV52540106;