dbSNP rs3771742: ENSG00000264324:n.*240-990T>C (chr2-74343527-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000451608.2(ENSG00000264324):n.*240-990T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,176 control chromosomes in the GnomAD database, including 1,555 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 0.12 ( 1555 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

ENSG00000264324
ENST00000451608.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.115

Publications

5 publications found

Variant links:

Genes affected

ENSG00000264324 (HGNC:):

ENSG00000264324 links:

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:

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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=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3 link	c.-518T>C		upstream_gene_variant		ENST00000394019.7	NP_597812.1	Q9BY07-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000264324	ENST00000451608.2 link	n.*240-990T>C		intron_variant	Intron 6 of 38	5		ENSP00000416453.2		E7EWF7
SLC4A5	ENST00000394019.7 link	c.-518T>C		upstream_gene_variant		5	NM_133478.3	ENSP00000377587.2		Q9BY07-3

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18791

AN:

152056

Hom.:

1553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.124

AC:

18796

AN:

152174

Hom.:

1555

Cov.:

AF XY:

0.127

AC XY:

9436

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.110

AC:

4573

AN:

41526

American (AMR)

AF:

0.105

AC:

1601

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

387

AN:

3464

East Asian (EAS)

AF:

0.470

AC:

2430

AN:

5170

South Asian (SAS)

AF:

0.208

AC:

1003

AN:

4812

European-Finnish (FIN)

AF:

0.101

AC:

1073

AN:

10592

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7215

AN:

68000

Other (OTH)

AF:

0.131

AC:

275

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

828

1656

2484

3312

4140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.113

Hom.:

1311

Bravo

AF:

0.126

Asia WGS

AF:

0.329

AC:

1139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.8

(source)

DANN

Benign

0.84

PhyloP100

0.12

PromoterAI

0.032

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over