NM_133478.3:c.2060-600G>A

Variant names:

• chr2-74242652-C-T
• rs8179526
• NM_133478.3:c.2060-600G>A

Variant summary

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

The NM_133478.3(SLC4A5):​c.2060-600G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,910 control chromosomes in the GnomAD database, including 15,689 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 0.45 (15689 hom., cov: 31)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2060-600G>A		intron_variant	Intron 19 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2060-600G>A		intron_variant	Intron 14 of 25		NP_067019.3
SLC4A5	NM_001386136.1	c.1712-600G>A		intron_variant	Intron 13 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2060-600G>A		intron_variant	Intron 19 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*2648-600G>A		intron_variant	Intron 24 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68272 AN: 151790 Hom.: 15685 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.450 AC: 68311 AN: 151910 Hom.: 15689 Cov.: 31 AF XY: 0.449 AC XY: 33361 AN XY: 74278

African (AFR) AF: 0.445 AC: 18424 AN: 41396

American (AMR) AF: 0.444 AC: 6777 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1509 AN: 5174

South Asian (SAS) AF: 0.227 AC: 1096 AN: 4822

European-Finnish (FIN) AF: 0.586 AC: 6185 AN: 10554

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31336 AN: 67914

Other (OTH) AF: 0.440 AC: 930 AN: 2112

Alfa AF: 0.448 Hom.: 28298

Bravo AF: 0.444

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		0.20
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: rs8179526; hg19: chr2-74469779; COSMIC: COSV61033001;