Genetic Variant SLC4A2:c.1450-4C>T (chr7-151070453-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003040.4(SLC4A2):c.1450-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 1,611,352 control chromosomes in the GnomAD database, including 1,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 134 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1457 hom. )

Consequence

SLC4A2
NM_003040.4 splice_region, intron

Scores

Splicing: ADA: 0.00008835

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.228

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4 link	c.1450-4C>T	splice_region_variant, intron_variant	Intron 10 of 22	ENST00000413384.7	NP_003031.3	P04920-1
SLC4A2	NM_001199692.3 link	c.1450-4C>T	splice_region_variant, intron_variant	Intron 10 of 22		NP_001186621.1	P04920-1Q59GF1
SLC4A2	NM_001199693.1 link	c.1423-4C>T	splice_region_variant, intron_variant	Intron 9 of 21		NP_001186622.1	P04920-3Q59GF1
SLC4A2	NM_001199694.2 link	c.1408-4C>T	splice_region_variant, intron_variant	Intron 9 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.1450-4C>T		splice_region_variant, intron_variant	Intron 10 of 22	1	NM_003040.4	ENSP00000405600.2		P04920-1

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

4778

AN:

152186

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00787

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0957

Gnomad SAS

AF:

0.0682

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0449

AC:

10966

AN:

244164

Hom.:

381

AF XY:

0.0480

AC XY:

6358

AN XY:

132576

show subpopulations

Gnomad AFR exome

AF:

0.00721

Gnomad AMR exome

AF:

0.0180

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.0714

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0378

Gnomad OTH exome

AF:

0.0464

GnomAD4 exome

AF:

0.0391

AC:

57111

AN:

1459048

Hom.:

1457

Cov.:

AF XY:

0.0409

AC XY:

29666

AN XY:

725766

show subpopulations

Gnomad4 AFR exome

AF:

0.00724

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.0994

Gnomad4 SAS exome

AF:

0.0712

Gnomad4 FIN exome

AF:

0.0263

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0469

GnomAD4 genome

AF:

0.0314

AC:

4780

AN:

152304

Hom.:

134

Cov.:

AF XY:

0.0324

AC XY:

2410

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00784

Gnomad4 AMR

AF:

0.0227

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.0957

Gnomad4 SAS

AF:

0.0679

Gnomad4 FIN

AF:

0.0208

Gnomad4 NFE

AF:

0.0351

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0324

Hom.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.1

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over