dbSNP rs11766855: SLC4A2:c.3471+55C>T (chr7-151075830-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 NM_003040.4(SLC4A2):c.3471+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,556,726 control chromosomes in the GnomAD database, including 26,524 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 ( 1803 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24721 hom. )

Consequence

SLC4A2
NM_003040.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

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:

ENSG00000244151 (HGNC:):

ENSG00000244151 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4 link	c.3471+55C>T	intron_variant	Intron 21 of 22	ENST00000413384.7	NP_003031.3	P04920-1
SLC4A2	NM_001199692.3 link	c.3471+55C>T	intron_variant	Intron 21 of 22		NP_001186621.1	P04920-1Q59GF1
SLC4A2	NM_001199693.1 link	c.3444+55C>T	intron_variant	Intron 20 of 21		NP_001186622.1	P04920-3Q59GF1
SLC4A2	NM_001199694.2 link	c.3429+55C>T	intron_variant	Intron 20 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.3471+55C>T		intron_variant	Intron 21 of 22	1	NM_003040.4	ENSP00000405600.2		P04920-1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22256

AN:

152022

Hom.:

1807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.181

AC:

254811

AN:

1404584

Hom.:

24721

Cov.:

AF XY:

0.184

AC XY:

127432

AN XY:

693044

show subpopulations

African (AFR)

AF:

0.0925

AC:

2971

AN:

32134

American (AMR)

AF:

0.0923

AC:

3744

AN:

40572

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

3658

AN:

23450

East Asian (EAS)

AF:

0.0155

AC:

603

AN:

39022

South Asian (SAS)

AF:

0.271

AC:

21762

AN:

80392

European-Finnish (FIN)

AF:

0.134

AC:

6764

AN:

50364

Middle Eastern (MID)

AF:

0.192

AC:

937

AN:

4890

European-Non Finnish (NFE)

AF:

0.190

AC:

204169

AN:

1075954

Other (OTH)

AF:

0.177

AC:

10203

AN:

57806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

10918

21835

32753

43670

54588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7270

14540

21810

29080

36350

<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:

0.146

AC:

22261

AN:

152142

Hom.:

1803

Cov.:

AF XY:

0.143

AC XY:

10627

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.102

AC:

4246

AN:

41506

American (AMR)

AF:

0.124

AC:

1891

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

548

AN:

3468

East Asian (EAS)

AF:

0.0168

AC:

AN:

5182

South Asian (SAS)

AF:

0.269

AC:

1291

AN:

4806

European-Finnish (FIN)

AF:

0.126

AC:

1337

AN:

10610

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12469

AN:

67958

Other (OTH)

AF:

0.147

AC:

310

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

954

1907

2861

3814

4768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.149

Hom.:

1384

Bravo

AF:

0.139

Asia WGS

AF:

0.152

AC:

532

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.033

(source)

DANN

Benign

0.64

PhyloP100

-1.9

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