2-74230591-A-C

Variant names:

• chr2-74230591-A-C
• rs10177833
• NM_133478.3:c.2847+645T>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.2847+645T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,938 control chromosomes in the GnomAD database, including 17,053 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 0.47 (17053 hom., cov: 31)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 28 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133478.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A5	NM_133478.3	MANE Select	c.2847+645T>G		intron	N/A	NP_597812.1
	SLC4A5	NM_021196.3		c.2847+645T>G		intron	N/A	NP_067019.3
	SLC4A5	NM_001386136.1		c.2499+645T>G		intron	N/A	NP_001373065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A5	ENST00000394019.7	TSL:5 MANE Select	c.2847+645T>G		intron	N/A	ENSP00000377587.2
	SLC4A5	ENST00000377632.5	TSL:1	c.2847+645T>G		intron	N/A	ENSP00000366859.1
	SLC4A5	ENST00000358683.8	TSL:1	c.2541+645T>G		intron	N/A	ENSP00000351513.4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71323 AN: 151820 Hom.: 17022 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.470 AC: 71390 AN: 151938 Hom.: 17053 Cov.: 31 AF XY: 0.474 AC XY: 35232 AN XY: 74262

African (AFR) AF: 0.512 AC: 21187 AN: 41400

American (AMR) AF: 0.480 AC: 7325 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3472

East Asian (EAS) AF: 0.610 AC: 3146 AN: 5156

South Asian (SAS) AF: 0.313 AC: 1511 AN: 4820

European-Finnish (FIN) AF: 0.563 AC: 5934 AN: 10546

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29098 AN: 67958

Other (OTH) AF: 0.470 AC: 995 AN: 2116

Alfa AF: 0.438 Hom.: 42911

Bravo AF: 0.471

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.83
PhyloP100		-0.081
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: rs10177833; hg19: chr2-74457718;