chr2-74241119-A-T

Variant names:

• chr2-74241119-A-T
• rs6731545
• NM_133478.3:c.2118+875T>A

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.2118+875T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 29)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 10 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=-0.82).

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.2118+875T>A		intron	N/A	NP_597812.1
	SLC4A5	NM_021196.3		c.2118+875T>A		intron	N/A	NP_067019.3
	SLC4A5	NM_001386136.1		c.1770+875T>A		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.2118+875T>A		intron	N/A	ENSP00000377587.2
	SLC4A5	ENST00000377632.5	TSL:1	c.2118+875T>A		intron	N/A	ENSP00000366859.1
	SLC4A5	ENST00000358683.8	TSL:1	c.1926+875T>A		intron	N/A	ENSP00000351513.4

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.73
PhyloP100		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6731545; hg19: chr2-74468246;