2-74255765-T-C

Variant names:

• chr2-74255765-T-C
• rs7602215
• NM_133478.3:c.1025+10A>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.1025+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,578 control chromosomes in the GnomAD database, including 23,120 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 0.20 (3455 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19665 hom.)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A5	NM_133478.3	MANE Select	c.1025+10A>G		intron	N/A	NP_597812.1	Q9BY07-3
	SLC4A5	NM_021196.3		c.1025+10A>G		intron	N/A	NP_067019.3	Q9BY07-1
	SLC4A5	NM_001386136.1		c.677+10A>G		intron	N/A	NP_001373065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A5	ENST00000394019.7	TSL:5 MANE Select	c.1025+10A>G		intron	N/A	ENSP00000377587.2	Q9BY07-3
	SLC4A5	ENST00000377632.5	TSL:1	c.1025+10A>G		intron	N/A	ENSP00000366859.1	Q9BY07-4
	SLC4A5	ENST00000358683.8	TSL:1	c.833+10A>G		intron	N/A	ENSP00000351513.4	Q9BY07-7

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29687 AN: 151964 Hom.: 3439 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.167 AC: 41795 AN: 250050 AF XY: 0.166

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.0883

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.385

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.155 AC: 226614 AN: 1461496 Hom.: 19665 Cov.: 32 AF XY: 0.155 AC XY: 112921 AN XY: 727018

African (AFR) AF: 0.310 AC: 10361 AN: 33472

American (AMR) AF: 0.0955 AC: 4271 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3048 AN: 26132

East Asian (EAS) AF: 0.373 AC: 14809 AN: 39684

South Asian (SAS) AF: 0.186 AC: 16043 AN: 86234

European-Finnish (FIN) AF: 0.113 AC: 6009 AN: 53396

Middle Eastern (MID) AF: 0.201 AC: 1155 AN: 5752

European-Non Finnish (NFE) AF: 0.144 AC: 160453 AN: 1111736

Other (OTH) AF: 0.173 AC: 10465 AN: 60372

GnomAD4 genome AF: 0.195 AC: 29728 AN: 152082 Hom.: 3455 Cov.: 32 AF XY: 0.194 AC XY: 14447 AN XY: 74338

African (AFR) AF: 0.307 AC: 12746 AN: 41466

American (AMR) AF: 0.145 AC: 2215 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3464

East Asian (EAS) AF: 0.364 AC: 1876 AN: 5154

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4812

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10604

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9692 AN: 67998

Other (OTH) AF: 0.188 AC: 396 AN: 2104

Alfa AF: 0.160 Hom.: 3971

Bravo AF: 0.206

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.72
DANN	Benign	0.56
PhyloP100		-2.7
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: rs7602215; hg19: chr2-74482892;