dbSNP rs12703112: SLC4A2:c.1147+95G>A (chr7-151068149-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003040.4(SLC4A2):c.1147+95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 961,352 control chromosomes in the GnomAD database, including 19,075 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 0.15 ( 2078 hom., cov: 33)

Exomes 𝑓: 0.20 ( 16997 hom. )

Consequence

SLC4A2
NM_003040.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.395

Publications

5 publications found

Variant links:

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]

SLC4A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4 link	c.1147+95G>A	intron_variant	Intron 8 of 22	ENST00000413384.7	NP_003031.3	P04920-1
SLC4A2	NM_001199692.3 link	c.1147+95G>A	intron_variant	Intron 8 of 22		NP_001186621.1	P04920-1Q59GF1
SLC4A2	NM_001199693.1 link	c.1120+95G>A	intron_variant	Intron 7 of 21		NP_001186622.1	P04920-3Q59GF1
SLC4A2	NM_001199694.2 link	c.1105+95G>A	intron_variant	Intron 7 of 21		NP_001186623.1	P04920-2Q59GF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7 link	c.1147+95G>A		intron_variant	Intron 8 of 22	1	NM_003040.4	ENSP00000405600.2		P04920-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23419

AN:

152098

Hom.:

2078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0886

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.196

AC:

158644

AN:

809136

Hom.:

16997

AF XY:

0.198

AC XY:

79303

AN XY:

399806

show subpopulations

African (AFR)

AF:

0.0817

AC:

1361

AN:

16660

American (AMR)

AF:

0.109

AC:

1091

AN:

9980

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

2413

AN:

14950

East Asian (EAS)

AF:

0.0235

AC:

620

AN:

26436

South Asian (SAS)

AF:

0.266

AC:

10809

AN:

40560

European-Finnish (FIN)

AF:

0.144

AC:

4473

AN:

30990

Middle Eastern (MID)

AF:

0.190

AC:

565

AN:

2968

European-Non Finnish (NFE)

AF:

0.207

AC:

130459

AN:

629334

Other (OTH)

AF:

0.184

AC:

6853

AN:

37258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6180

12359

18539

24718

30898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3962

7924

11886

15848

19810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.154

AC:

23430

AN:

152216

Hom.:

2078

Cov.:

AF XY:

0.150

AC XY:

11143

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0886

AC:

3681

AN:

41550

American (AMR)

AF:

0.126

AC:

1923

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3464

East Asian (EAS)

AF:

0.0201

AC:

104

AN:

5186

South Asian (SAS)

AF:

0.270

AC:

1302

AN:

4824

European-Finnish (FIN)

AF:

0.134

AC:

1417

AN:

10566

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13989

AN:

68000

Other (OTH)

AF:

0.160

AC:

339

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

998

1996

2993

3991

4989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.173

Hom.:

3178

Bravo

AF:

0.145

Asia WGS

AF:

0.157

AC:

548

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.76

(source)

DANN

Benign

0.68

PhyloP100

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over