Genetic Variant SLC4A5:c.80-25C>G (chr2-74304705-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_133478.3(SLC4A5):c.80-25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,586,378 control chromosomes in the GnomAD database, including 870 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 0.024 ( 67 hom., cov: 32)

Exomes 𝑓: 0.030 ( 803 hom. )

Consequence

SLC4A5
NM_133478.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.743

Publications

2 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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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=-0.83).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.024 (3651/152282) while in subpopulation NFE AF = 0.034 (2312/68010). AF 95% confidence interval is 0.0328. There are 67 homozygotes in GnomAd4. There are 1826 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3 link	c.80-25C>G		intron_variant	Intron 6 of 30	ENST00000394019.7	NP_597812.1	Q9BY07-3
SLC4A5	NM_021196.3 link	c.80-25C>G		intron_variant	Intron 1 of 25		NP_067019.3	Q9BY07-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7 link	c.80-25C>G		intron_variant	Intron 6 of 30	5	NM_133478.3	ENSP00000377587.2		Q9BY07-3
ENSG00000264324	ENST00000451608.2 link	n.*668-25C>G		intron_variant	Intron 11 of 38	5		ENSP00000416453.2		E7EWF7

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3653

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00512

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00913

Gnomad FIN

AF:

0.0689

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0265

AC:

6219

AN:

234500

AF XY:

0.0261

show subpopulations

Gnomad AFR exome

AF:

0.00499

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0741

Gnomad NFE exome

AF:

0.0338

Gnomad OTH exome

AF:

0.0281

GnomAD4 exome

AF:

0.0304

AC:

43542

AN:

1434096

Hom.:

803

Cov.:

AF XY:

0.0297

AC XY:

21078

AN XY:

710634

show subpopulations

African (AFR)

AF:

0.00465

AC:

150

AN:

32250

American (AMR)

AF:

0.0143

AC:

572

AN:

40108

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

383

AN:

24964

East Asian (EAS)

AF:

0.00

AC:

AN:

39044

South Asian (SAS)

AF:

0.00846

AC:

699

AN:

82612

European-Finnish (FIN)

AF:

0.0711

AC:

3770

AN:

52988

Middle Eastern (MID)

AF:

0.0176

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.0331

AC:

36294

AN:

1097332

Other (OTH)

AF:

0.0266

AC:

1575

AN:

59166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2195

4391

6586

8782

10977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0240

AC:

3651

AN:

152282

Hom.:

Cov.:

AF XY:

0.0245

AC XY:

1826

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00510

AC:

212

AN:

41558

American (AMR)

AF:

0.0141

AC:

215

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00934

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0689

AC:

732

AN:

10620

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0340

AC:

2312

AN:

68010

Other (OTH)

AF:

0.0194

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

183

366

549

732

915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0285

Hom.:

Bravo

AF:

0.0190

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.6

(source)

DANN

Benign

0.60

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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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2-74304705-G-C

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