2-74335013-G-C

Variant names:

• chr2-74335013-G-C
• rs13387588
• NM_133478.3:c.-220-836C>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.-220-836C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,010 control chromosomes in the GnomAD database, including 4,697 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 0.21 (4697 hom., cov: 32)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.-220-836C>G		intron_variant	Intron 3 of 30	ENST00000394019.7	NP_597812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.-220-836C>G		intron_variant	Intron 3 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*369-836C>G		intron_variant	Intron 8 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31671 AN: 151892 Hom.: 4687 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.209 AC: 31711 AN: 152010 Hom.: 4697 Cov.: 32 AF XY: 0.208 AC XY: 15483 AN XY: 74322

African (AFR) AF: 0.393 AC: 16278 AN: 41384

American (AMR) AF: 0.144 AC: 2204 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2410 AN: 5158

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4816

European-Finnish (FIN) AF: 0.102 AC: 1084 AN: 10588

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7563 AN: 67980

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.0633 Hom.: 91

Bravo AF: 0.223

Asia WGS AF: 0.354 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.60
PhyloP100		-1.1
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: rs13387588; hg19: chr2-74562140;