Genetic Variant SLC4A5:c.3332-27A>G (chr2-74221528-T-C) – 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.3332-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,607,558 control chromosomes in the GnomAD database, including 82,691 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 0.27 ( 6645 hom., cov: 32)

Exomes 𝑓: 0.31 ( 76046 hom. )

Consequence

SLC4A5
NM_133478.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.411

Publications

15 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC4A5	NM_133478.3 link	c.3332-27A>G	intron_variant	Intron 29 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3 link	c.3380-27A>G	intron_variant	Intron 25 of 25		NP_067019.3
SLC4A5	NM_001386136.1 link	c.2984-27A>G	intron_variant	Intron 23 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7 link	c.3332-27A>G		intron_variant	Intron 29 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2 link	n.*3984-27A>G		intron_variant	Intron 35 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41819

AN:

152056

Hom.:

6643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.292

GnomAD2 exomes

AF:

0.277

AC:

69577

AN:

251190

AF XY:

0.280

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.313

AC:

455999

AN:

1455384

Hom.:

76046

Cov.:

AF XY:

0.312

AC XY:

225672

AN XY:

724418

show subpopulations

African (AFR)

AF:

0.144

AC:

4823

AN:

33404

American (AMR)

AF:

0.153

AC:

6838

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9812

AN:

26090

East Asian (EAS)

AF:

0.102

AC:

4051

AN:

39676

South Asian (SAS)

AF:

0.187

AC:

16120

AN:

86154

European-Finnish (FIN)

AF:

0.485

AC:

25902

AN:

53376

Middle Eastern (MID)

AF:

0.364

AC:

2098

AN:

5756

European-Non Finnish (NFE)

AF:

0.332

AC:

367624

AN:

1106062

Other (OTH)

AF:

0.311

AC:

18731

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

12883

25766

38649

51532

64415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11516

23032

34548

46064

57580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.275

AC:

41828

AN:

152174

Hom.:

6645

Cov.:

AF XY:

0.279

AC XY:

20767

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.149

AC:

6189

AN:

41520

American (AMR)

AF:

0.221

AC:

3381

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1293

AN:

3468

East Asian (EAS)

AF:

0.125

AC:

644

AN:

5172

South Asian (SAS)

AF:

0.176

AC:

848

AN:

4830

European-Finnish (FIN)

AF:

0.504

AC:

5333

AN:

10582

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23045

AN:

67986

Other (OTH)

AF:

0.297

AC:

629

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1503

3006

4509

6012

7515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.308

Hom.:

10289

Bravo

AF:

0.248

Asia WGS

AF:

0.188

AC:

654

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.5

(source)

DANN

Benign

0.61

PhyloP100

-0.41

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

Publications

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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