dbSNP rs33966546: SLC4A2:c.-290C>T (chr7-151062891-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000461735.1(SLC4A2):c.-290C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,389,776 control chromosomes in the GnomAD database, including 49,090 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 0.27 ( 5917 hom., cov: 32)

Exomes 𝑓: 0.26 ( 43173 hom. )

Consequence

SLC4A2
ENST00000461735.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.838

Publications

6 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:

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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=-0.77).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4 link	c.51+853C>T	intron_variant	Intron 2 of 22	ENST00000413384.7	NP_003031.3	P04920-1
SLC4A2	NM_001199694.2 link	c.-290C>T	5_prime_UTR_variant	Exon 1 of 22		NP_001186623.1	P04920-2Q59GF1
SLC4A2	NM_001199692.3 link	c.51+853C>T	intron_variant	Intron 2 of 22		NP_001186621.1	P04920-1Q59GF1
SLC4A2	NM_001199693.1 link	c.24+228C>T	intron_variant	Intron 1 of 21		NP_001186622.1	P04920-3Q59GF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7 link	c.51+853C>T		intron_variant	Intron 2 of 22	1	NM_003040.4	ENSP00000405600.2		P04920-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41140

AN:

151848

Hom.:

5904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.261

AC:

323117

AN:

1237810

Hom.:

43173

Cov.:

AF XY:

0.259

AC XY:

155030

AN XY:

598026

show subpopulations

African (AFR)

AF:

0.234

AC:

5795

AN:

24752

American (AMR)

AF:

0.488

AC:

7227

AN:

14806

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

3934

AN:

17668

East Asian (EAS)

AF:

0.197

AC:

5746

AN:

29188

South Asian (SAS)

AF:

0.198

AC:

11467

AN:

57980

European-Finnish (FIN)

AF:

0.297

AC:

8709

AN:

29304

Middle Eastern (MID)

AF:

0.228

AC:

789

AN:

3466

European-Non Finnish (NFE)

AF:

0.264

AC:

266498

AN:

1009416

Other (OTH)

AF:

0.253

AC:

12952

AN:

51230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11996

23992

35988

47984

59980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9558

19116

28674

38232

47790

<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:

0.271

AC:

41163

AN:

151966

Hom.:

5917

Cov.:

AF XY:

0.272

AC XY:

20194

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.239

AC:

9915

AN:

41458

American (AMR)

AF:

0.406

AC:

6205

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

808

AN:

3470

East Asian (EAS)

AF:

0.215

AC:

1103

AN:

5142

South Asian (SAS)

AF:

0.193

AC:

931

AN:

4814

European-Finnish (FIN)

AF:

0.298

AC:

3152

AN:

10582

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18069

AN:

67906

Other (OTH)

AF:

0.270

AC:

570

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1544

3088

4632

6176

7720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.280

Hom.:

776

Bravo

AF:

0.286

Asia WGS

AF:

0.209

AC:

724

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.9

(source)

DANN

Benign

0.89

PhyloP100

-0.84

PromoterAI

0.083

Neutral

(source)

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

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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