NM_133478.3:c.3332-27A>G

Variant names:

• chr2-74221528-T-C
• rs7587117
• NM_133478.3:c.3332-27A>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.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
• Publications: 15 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A5	NM_133478.3	MANE Select	c.3332-27A>G		intron	N/A	NP_597812.1
	SLC4A5	NM_021196.3		c.3380-27A>G		intron	N/A	NP_067019.3
	SLC4A5	NM_001386136.1		c.2984-27A>G		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.3332-27A>G		intron	N/A	ENSP00000377587.2
	SLC4A5	ENST00000377632.5	TSL:1	c.3089-27A>G		intron	N/A	ENSP00000366859.1
	SLC4A5	ENST00000358683.8	TSL:1	c.3026-27A>G		intron	N/A	ENSP00000351513.4

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

GnomAD2 exomes AF: 0.277 AC: 69577 AN: 251190 AF XY: 0.280

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 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

African (AFR) AF: 0.144 AC: 4823 AN: 33404

American (AMR) AF: 0.153 AC: 6838 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9812 AN: 26090

East Asian (EAS) AF: 0.102 AC: 4051 AN: 39676

South Asian (SAS) AF: 0.187 AC: 16120 AN: 86154

European-Finnish (FIN) AF: 0.485 AC: 25902 AN: 53376

Middle Eastern (MID) AF: 0.364 AC: 2098 AN: 5756

European-Non Finnish (NFE) AF: 0.332 AC: 367624 AN: 1106062

Other (OTH) AF: 0.311 AC: 18731 AN: 60158

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

African (AFR) AF: 0.149 AC: 6189 AN: 41520

American (AMR) AF: 0.221 AC: 3381 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3468

East Asian (EAS) AF: 0.125 AC: 644 AN: 5172

South Asian (SAS) AF: 0.176 AC: 848 AN: 4830

European-Finnish (FIN) AF: 0.504 AC: 5333 AN: 10582

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23045 AN: 67986

Other (OTH) AF: 0.297 AC: 629 AN: 2116

Alfa AF: 0.308 Hom.: 10289

Bravo AF: 0.248

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		-0.41
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: rs7587117; hg19: chr2-74448655;