rs12991424

Positions:

• chr2-74304705-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_133478.3(SLC4A5):​c.80-25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,586,378 control chromosomes in the GnomAD database, including 870 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 0.024 (67 hom., cov: 32)
  • Exomes 𝑓: 0.030 (803 hom.)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.024 (3651/152282) while in subpopulation NFE AF= 0.034 (2312/68010). AF 95% confidence interval is 0.0328. There are 67 homozygotes in gnomad4. There are 1826 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.80-25C>G		intron_variant		ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.80-25C>G		intron_variant			NP_067019.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.80-25C>G		intron_variant		5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*668-25C>G		intron_variant		5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3653 AN: 152164 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00913

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.0265 AC: 6219 AN: 234500 Hom.: 134 AF XY: 0.0261 AC XY: 3316 AN XY: 126852

Gnomad AFR exome AF: 0.00499

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00766

Gnomad FIN exome AF: 0.0741

Gnomad NFE exome AF: 0.0338

Gnomad OTH exome AF: 0.0281

GnomAD4 exome AF: 0.0304 AC: 43542 AN: 1434096 Hom.: 803 Cov.: 29 AF XY: 0.0297 AC XY: 21078 AN XY: 710634

Gnomad4 AFR exome AF: 0.00465

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00846

Gnomad4 FIN exome AF: 0.0711

Gnomad4 NFE exome AF: 0.0331

Gnomad4 OTH exome AF: 0.0266

GnomAD4 genome AF: 0.0240 AC: 3651 AN: 152282 Hom.: 67 Cov.: 32 AF XY: 0.0245 AC XY: 1826 AN XY: 74466

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0340

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0285 Hom.: 21

Bravo AF: 0.0190

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs12991424; hg19: chr2-74531832;