dbSNP rs1493193: SLC4A8:c.*5127C>A (chr12-51512565-C-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_001039960.3(SLC4A8):c.*5127C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,402 control chromosomes in the GnomAD database, including 65,411 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 0.93 ( 65335 hom., cov: 31)

Exomes 𝑓: 0.95 ( 76 hom. )

Consequence

SLC4A8
NM_001039960.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.122

Publications

2 publications found

Variant links:

Genes affected

SLC4A8 (HGNC:11034): (solute carrier family 4 member 8) The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

SLC4A8 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SLC4A8 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A8	NM_001039960.3 link	c.*5127C>A		3_prime_UTR_variant	Exon 25 of 25	ENST00000453097.7	NP_001035049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A8	ENST00000453097.7 link	c.*5127C>A		3_prime_UTR_variant	Exon 25 of 25	1	NM_001039960.3	ENSP00000405812.2
SLC4A8	ENST00000358657.7 link	c.*5127C>A		3_prime_UTR_variant	Exon 25 of 25	1		ENSP00000351483.4

Frequencies

GnomAD3 genomes

AF:

0.926

AC:

140862

AN:

152118

Hom.:

65285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.991

Gnomad AMR

AF:

0.899

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

0.918

Gnomad SAS

AF:

0.900

Gnomad FIN

AF:

0.950

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.945

Gnomad OTH

AF:

0.926

GnomAD4 exome

AF:

0.952

AC:

158

AN:

166

Hom.:

Cov.:

AF XY:

0.935

AC XY:

101

AN XY:

108

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.944

AC:

119

AN:

126

Other (OTH)

AF:

0.938

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.926

AC:

140969

AN:

152236

Hom.:

65335

Cov.:

AF XY:

0.925

AC XY:

68833

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.898

AC:

37267

AN:

41518

American (AMR)

AF:

0.898

AC:

13735

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.975

AC:

3386

AN:

3472

East Asian (EAS)

AF:

0.919

AC:

4765

AN:

5184

South Asian (SAS)

AF:

0.899

AC:

4325

AN:

4812

European-Finnish (FIN)

AF:

0.950

AC:

10075

AN:

10608

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.945

AC:

64293

AN:

68028

Other (OTH)

AF:

0.926

AC:

1959

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

538

1076

1614

2152

2690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.933

Hom.:

11721

Bravo

AF:

0.921

Asia WGS

AF:

0.899

AC:

3128

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

(source)

DANN

Benign

0.69

PhyloP100

0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over