2-74241119-A-G

Variant names:

• chr2-74241119-A-G
• rs6731545
• NM_133478.3:c.2118+875T>C

Variant summary

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

The NM_133478.3(SLC4A5):​c.2118+875T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,736 control chromosomes in the GnomAD database, including 32,822 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 0.64 (32822 hom., cov: 29)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2118+875T>C		intron_variant	Intron 20 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2118+875T>C		intron_variant	Intron 15 of 25		NP_067019.3
SLC4A5	NM_001386136.1	c.1770+875T>C		intron_variant	Intron 14 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2118+875T>C		intron_variant	Intron 20 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*2706+875T>C		intron_variant	Intron 25 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97444 AN: 151616 Hom.: 32775 Cov.: 29

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.643 AC: 97544 AN: 151736 Hom.: 32822 Cov.: 29 AF XY: 0.642 AC XY: 47599 AN XY: 74120

African (AFR) AF: 0.847 AC: 35023 AN: 41372

American (AMR) AF: 0.652 AC: 9932 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1853 AN: 3466

East Asian (EAS) AF: 0.692 AC: 3555 AN: 5134

South Asian (SAS) AF: 0.391 AC: 1880 AN: 4806

European-Finnish (FIN) AF: 0.635 AC: 6672 AN: 10502

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36839 AN: 67914

Other (OTH) AF: 0.612 AC: 1287 AN: 2102

Alfa AF: 0.590 Hom.: 5692

Bravo AF: 0.662

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.7
DANN	Benign	0.78
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6731545; hg19: chr2-74468246;