chr2-74222998-T-C

Variant names:

• chr2-74222998-T-C
• rs6745054
• NM_133478.3:c.3247-46A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133478.3(SLC4A5):​c.3247-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,356,192 control chromosomes in the GnomAD database, including 30,310 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 0.29 (9780 hom., cov: 31)
  • Exomes 𝑓: 0.14 (20530 hom.)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 8 publications found

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]

ENSG00000264324 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.3247-46A>G		intron_variant	Intron 28 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.3295-46A>G		intron_variant	Intron 24 of 25		NP_067019.3
SLC4A5	NM_001386136.1	c.2899-46A>G		intron_variant	Intron 22 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.3247-46A>G		intron_variant	Intron 28 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*3899-46A>G		intron_variant	Intron 34 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43238 AN: 151446 Hom.: 9744 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.242

GnomAD2 exomes AF: 0.261 AC: 42006 AN: 160688 AF XY: 0.240

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.0872

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.142 AC: 171490 AN: 1204636 Hom.: 20530 Cov.: 16 AF XY: 0.140 AC XY: 84783 AN XY: 604310

African (AFR) AF: 0.596 AC: 14918 AN: 25014

American (AMR) AF: 0.473 AC: 14071 AN: 29738

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2272 AN: 21192

East Asian (EAS) AF: 0.461 AC: 17057 AN: 36992

South Asian (SAS) AF: 0.160 AC: 11260 AN: 70578

European-Finnish (FIN) AF: 0.0858 AC: 4238 AN: 49422

Middle Eastern (MID) AF: 0.111 AC: 560 AN: 5030

European-Non Finnish (NFE) AF: 0.107 AC: 98398 AN: 915840

Other (OTH) AF: 0.171 AC: 8716 AN: 50830

GnomAD4 genome AF: 0.286 AC: 43323 AN: 151556 Hom.: 9780 Cov.: 31 AF XY: 0.284 AC XY: 21046 AN XY: 74102

African (AFR) AF: 0.595 AC: 24523 AN: 41218

American (AMR) AF: 0.364 AC: 5551 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3464

East Asian (EAS) AF: 0.488 AC: 2515 AN: 5150

South Asian (SAS) AF: 0.184 AC: 887 AN: 4808

European-Finnish (FIN) AF: 0.0833 AC: 875 AN: 10506

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7965 AN: 67876

Other (OTH) AF: 0.240 AC: 503 AN: 2094

Alfa AF: 0.181 Hom.: 12705

Bravo AF: 0.330

Asia WGS AF: 0.322 AC: 1108 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.69
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6745054; hg19: chr2-74450125; COSMIC: COSV61034666;