2-74221528-T-C

Position:

• chr2-74221528-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133478.3(SLC4A5):​c.3332-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,607,558 control chromosomes in the GnomAD database, including 82,691 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 0.27 (6645 hom., cov: 32)
  • Exomes 𝑓: 0.31 (76046 hom.)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.3332-27A>G		intron_variant		ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.3380-27A>G		intron_variant			NP_067019.3
SLC4A5	NM_001386136.1	c.2984-27A>G		intron_variant			NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.3332-27A>G		intron_variant		5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*3984-27A>G		intron_variant		5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41819 AN: 152056 Hom.: 6643 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.292

GnomAD3 exomes AF: 0.277 AC: 69577 AN: 251190 Hom.: 11294 AF XY: 0.280 AC XY: 38018 AN XY: 135780

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.313 AC: 455999 AN: 1455384 Hom.: 76046 Cov.: 31 AF XY: 0.312 AC XY: 225672 AN XY: 724418

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.275 AC: 41828 AN: 152174 Hom.: 6645 Cov.: 32 AF XY: 0.279 AC XY: 20767 AN XY: 74402

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.297

Alfa AF: 0.317 Hom.: 8391

Bravo AF: 0.248

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs7587117; hg19: chr2-74448655;