dbSNP rs2069442: SLC4A2:c.-64+837G>C (chr7-151058118-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000483786.5(SLC4A2):c.-64+837G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 555,224 control chromosomes in the GnomAD database, including 24,798 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 0.32 ( 8183 hom., cov: 34)

Exomes 𝑓: 0.28 ( 16615 hom. )

Consequence

SLC4A2
ENST00000483786.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.353

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:

CDK5 (HGNC:1774): (cyclin dependent kinase 5) This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

CDK5 links:

Genome browser will be placed here

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 (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CDK5	NM_004935.4 link	c.-270C>G	upstream_gene_variant	ENST00000485972.6	NP_004926.1	Q00535-1A0A090N7W4
SLC4A2	NM_001199692.3 link	c.-1134G>C	upstream_gene_variant		NP_001186621.1	P04920-1Q59GF1
CDK5	NM_001164410.3 link	c.-270C>G	upstream_gene_variant		NP_001157882.1	Q00535-2A0A0S2Z355

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6 link	c.-270C>G		upstream_gene_variant		1	NM_004935.4	ENSP00000419782.1		Q00535-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48668

AN:

152120

Hom.:

8170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.281

AC:

113309

AN:

402988

Hom.:

16615

Cov.:

AF XY:

0.280

AC XY:

59143

AN XY:

211594

show subpopulations

Gnomad4 AFR exome

AF:

0.393

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.320

AC:

48708

AN:

152236

Hom.:

8183

Cov.:

AF XY:

0.323

AC XY:

24045

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.309

Alfa

AF:

0.308

Hom.:

935

Bravo

AF:

0.341

Asia WGS

AF:

0.314

AC:

1091

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

DANN

Benign

0.85

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

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