Genetic Variant NM_133478.3:c.2187C>T (chr2-74239467-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_133478.3(SLC4A5):c.2187C>T(p.Gly729Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,613,660 control chromosomes in the GnomAD database, including 131,273 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 0.34 ( 10268 hom., cov: 32)

Exomes 𝑓: 0.40 ( 121005 hom. )

Consequence

SLC4A5
NM_133478.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

Publications

22 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=-2.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3 link	c.2187C>T	p.Gly729Gly	synonymous_variant	Exon 21 of 31	ENST00000394019.7	NP_597812.1	Q9BY07-3
SLC4A5	NM_021196.3 link	c.2187C>T	p.Gly729Gly	synonymous_variant	Exon 16 of 26		NP_067019.3	Q9BY07-1
SLC4A5	NM_001386136.1 link	c.1839C>T	p.Gly613Gly	synonymous_variant	Exon 15 of 25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC4A5	ENST00000394019.7 link	c.2187C>T	p.Gly729Gly	synonymous_variant	Exon 21 of 31	5	NM_133478.3	ENSP00000377587.2	Q9BY07-3
ENSG00000264324	ENST00000451608.2 link	n.*2775C>T		non_coding_transcript_exon_variant	Exon 26 of 39	5		ENSP00000416453.2	E7EWF7
ENSG00000264324	ENST00000451608.2 link	n.*2775C>T		3_prime_UTR_variant	Exon 26 of 39	5		ENSP00000416453.2	E7EWF7

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52053

AN:

151942

Hom.:

10270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.350

GnomAD2 exomes

AF:

0.342

AC:

85998

AN:

251398

AF XY:

0.344

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.396

AC:

578511

AN:

1461600

Hom.:

121005

Cov.:

AF XY:

0.392

AC XY:

284858

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.184

AC:

6145

AN:

33468

American (AMR)

AF:

0.190

AC:

8480

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

11267

AN:

26132

East Asian (EAS)

AF:

0.143

AC:

5667

AN:

39700

South Asian (SAS)

AF:

0.198

AC:

17092

AN:

86246

European-Finnish (FIN)

AF:

0.546

AC:

29181

AN:

53414

Middle Eastern (MID)

AF:

0.387

AC:

2230

AN:

5758

European-Non Finnish (NFE)

AF:

0.427

AC:

474711

AN:

1111794

Other (OTH)

AF:

0.393

AC:

23738

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

19201

38403

57604

76806

96007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14092

28184

42276

56368

70460

<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:

0.342

AC:

52058

AN:

152060

Hom.:

10268

Cov.:

AF XY:

0.343

AC XY:

25476

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.190

AC:

7890

AN:

41498

American (AMR)

AF:

0.275

AC:

4198

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

1498

AN:

3470

East Asian (EAS)

AF:

0.188

AC:

974

AN:

5170

South Asian (SAS)

AF:

0.185

AC:

889

AN:

4816

European-Finnish (FIN)

AF:

0.568

AC:

6002

AN:

10574

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.433

AC:

29404

AN:

67952

Other (OTH)

AF:

0.353

AC:

744

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1662

3325

4987

6650

8312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.388

Hom.:

50041

Bravo

AF:

0.314

Asia WGS

AF:

0.227

AC:

794

AN:

3478

EpiCase

AF:

0.421

EpiControl

AF:

0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.7

(source)

DANN

Benign

0.79

PhyloP100

-2.1

Mutation Taster

=98/2

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