7-151064628-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_003040.4(SLC4A2):c.320G>A(p.Arg107Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,613,592 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (7 hom.)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.82

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SLC4A2
• BP4: Computational evidence support a benign effect (MetaRNN=0.009216309).
• BP6: Variant 7-151064628-G-A is Benign according to our data. Variant chr7-151064628-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.320G>A	p.Arg107Gln	missense_variant	4/23	ENST00000413384.7
SLC4A2	NM_001199692.3	c.320G>A	p.Arg107Gln	missense_variant	4/23
SLC4A2	NM_001199693.1	c.293G>A	p.Arg98Gln	missense_variant	3/22
SLC4A2	NM_001199694.2	c.278G>A	p.Arg93Gln	missense_variant	3/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.320G>A	p.Arg107Gln	missense_variant	4/23	1	NM_003040.4	P1

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 302 AN: 152146 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00145 AC: 360 AN: 247496 Hom.: 1 AF XY: 0.00150 AC XY: 202 AN XY: 134438

Gnomad AFR exome AF: 0.000812

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000458

Gnomad FIN exome AF: 0.000464

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00270 AC: 3952 AN: 1461328 Hom.: 7 Cov.: 36 AF XY: 0.00267 AC XY: 1944 AN XY: 726934

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000487

Gnomad4 FIN exome AF: 0.000506

Gnomad4 NFE exome AF: 0.00327

Gnomad4 OTH exome AF: 0.00320

GnomAD4 genome AF: 0.00199 AC: 303 AN: 152264 Hom.: 2 Cov.: 33 AF XY: 0.00181 AC XY: 135 AN XY: 74460

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00350

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00286 Hom.: 4

Bravo AF: 0.00190

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00157 AC: 190

EpiCase AF: 0.00360

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

SLC4A2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.031	T;T;T;T;.;.;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.95	D;.;D;D;D;D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.0092	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	0.91	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.052	T;T;T;T;T;D;T;T
Sift4G	Pathogenic	0.0	D;T;T;T;T;D;T;T
Polyphen		0.028, 0.048	.;B;B;.;.;.;.;B
Vest4		0.20, 0.17, 0.20, 0.18
MVP		0.66
MPC		0.66
ClinPred		0.016	T
GERP RS		4.4
Varity_R		0.059
gMVP		0.27

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: rs145741704; hg19: chr7-150761715; COSMIC: COSV59656232; COSMIC: COSV59656232;