dbSNP rs8179526: SLC4A5:c.2060-600G>A (chr2-74242652-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_133478.3(SLC4A5):c.2060-600G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,910 control chromosomes in the GnomAD database, including 15,689 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 0.45 ( 15689 hom., cov: 31)

Consequence

SLC4A5
NM_133478.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204

Publications

16 publications found

Variant links:

Genes affected

SLC4A5 (HGNC:18168): (solute carrier family 4 member 5) This gene encodes a member of the sodium bicarbonate cotransporter (NBC) family, part of the bicarbonate transporter superfamily. Sodium bicarbonate cotransporters are involved in intracellular pH regulation and electroneural or electrogenic sodium bicarbonate transport. This protein is thought to be an integral membrane protein. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

SLC4A5 links:

ENSG00000264324 (HGNC:):

ENSG00000264324 links:

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new If you want to explore the variant's impact on the transcript NM_133478.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133478.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC4A5	NM_133478.3	MANE Select	c.2060-600G>A	intron	N/A	NP_597812.1	Q9BY07-3
SLC4A5	NM_021196.3		c.2060-600G>A	intron	N/A	NP_067019.3	Q9BY07-1
SLC4A5	NM_001386136.1		c.1712-600G>A	intron	N/A	NP_001373065.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC4A5	ENST00000394019.7	TSL:5 MANE Select	c.2060-600G>A	intron	N/A	ENSP00000377587.2	Q9BY07-3
SLC4A5	ENST00000377632.5	TSL:1	c.2060-600G>A	intron	N/A	ENSP00000366859.1	Q9BY07-4
SLC4A5	ENST00000358683.8	TSL:1	c.1868-600G>A	intron	N/A	ENSP00000351513.4	Q9BY07-7

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68272

AN:

151790

Hom.:

15685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.450

AC:

68311

AN:

151910

Hom.:

15689

Cov.:

AF XY:

0.449

AC XY:

33361

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.445

AC:

18424

AN:

41396

American (AMR)

AF:

0.444

AC:

6777

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

1563

AN:

3468

East Asian (EAS)

AF:

0.292

AC:

1509

AN:

5174

South Asian (SAS)

AF:

0.227

AC:

1096

AN:

4822

European-Finnish (FIN)

AF:

0.586

AC:

6185

AN:

10554

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31336

AN:

67914

Other (OTH)

AF:

0.440

AC:

930

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1876

3753

5629

7506

9382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.448

Hom.:

28298

Bravo

AF:

0.444

Asia WGS

AF:

0.316

AC:

1100

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.2

(source)

DANN

Benign

0.48

PhyloP100

0.20

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over