chr7-151064879-G-A

Variant names:

• chr7-151064879-G-A
• rs142748851
• NM_003040.4:c.491G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003040.4(SLC4A2):​c.491G>A​(p.Arg164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,613,976 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025209844).

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.491G>A	p.Arg164Gln	missense	Exon 5 of 23	NP_003031.3
	SLC4A2	NM_001199692.3		c.491G>A	p.Arg164Gln	missense	Exon 5 of 23	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.464G>A	p.Arg155Gln	missense	Exon 4 of 22	NP_001186622.1	Q59GF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.491G>A	p.Arg164Gln	missense	Exon 5 of 23	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.491G>A	p.Arg164Gln	missense	Exon 5 of 23	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.449G>A	p.Arg150Gln	missense	Exon 4 of 22	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000247 AC: 62 AN: 251260 AF XY: 0.000191

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000200 AC: 293 AN: 1461700 Hom.: 1 Cov.: 34 AF XY: 0.000202 AC XY: 147 AN XY: 727176

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.000738 AC: 33 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000204 AC: 227 AN: 1111978

Other (OTH) AF: 0.000265 AC: 16 AN: 60390

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152276 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74468

African (AFR) AF: 0.000265 AC: 11 AN: 41562

American (AMR) AF: 0.000523 AC: 8 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68004

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.000287

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000222 AC: 27

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.28
Sift	Benign	0.50	T
Sift4G	Benign	0.56	T
Polyphen		0.99	D
Vest4		0.34
MVP		0.84
MPC		1.4
ClinPred		0.023	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.31
Mutation Taster		=83/17	polymorphism

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: rs142748851; hg19: chr7-150761966;