2-74222998-T-G

Variant names:

• chr2-74222998-T-G
• rs6745054
• NM_133478.3:c.3247-46A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133478.3(SLC4A5):​c.3247-46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,282 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.3247-46A>C		intron_variant	Intron 28 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.3295-46A>C		intron_variant	Intron 24 of 25		NP_067019.3
SLC4A5	NM_001386136.1	c.2899-46A>C		intron_variant	Intron 22 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.3247-46A>C		intron_variant	Intron 28 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*3899-46A>C		intron_variant	Intron 34 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000249 AC: 3 AN: 1206282 Hom.: 0 Cov.: 16 AF XY: 0.00000165 AC XY: 1 AN XY: 605116

African (AFR) AF: 0.00 AC: 0 AN: 25084

American (AMR) AF: 0.00 AC: 0 AN: 29840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21220

East Asian (EAS) AF: 0.00 AC: 0 AN: 37070

South Asian (SAS) AF: 0.00 AC: 0 AN: 70670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5036

European-Non Finnish (NFE) AF: 0.00000218 AC: 2 AN: 917004

Other (OTH) AF: 0.0000196 AC: 1 AN: 50900

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.68
PhyloP100		0.14

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: rs6745054; hg19: chr2-74450125;