rs17009792

Variant names:

• chr2-74262196-C-T
• rs17009792
• NM_133478.3:c.752G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133478.3(SLC4A5):​c.752G>A​(p.Ser251Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,541,390 control chromosomes in the GnomAD database, including 1,690 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.087 (560 hom., cov: 28)
  • Exomes 𝑓: 0.030 (1130 hom.)
• Consequence: SLC4A5 NM_133478.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.775
• Publications: 16 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 (MetaRNN=0.0013481379).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.752G>A	p.Ser251Asn	missense_variant	Exon 11 of 31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.752G>A	p.Ser251Asn	missense_variant	Exon 6 of 26		NP_067019.3
SLC4A5	NM_001386136.1	c.404G>A	p.Ser135Asn	missense_variant	Exon 5 of 25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.752G>A	p.Ser251Asn	missense_variant	Exon 11 of 31	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*1340G>A		non_coding_transcript_exon_variant	Exon 16 of 39	5		ENSP00000416453.2
ENSG00000264324	ENST00000451608.2	n.*1340G>A		3_prime_UTR_variant	Exon 16 of 39	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 9339 AN: 107826 Hom.: 558 Cov.: 28

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0800

GnomAD2 exomes AF: 0.0367 AC: 9102 AN: 247882 AF XY: 0.0369

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0143

Gnomad ASJ exome AF: 0.0682

Gnomad EAS exome AF: 0.00450

Gnomad FIN exome AF: 0.0211

Gnomad NFE exome AF: 0.0248

Gnomad OTH exome AF: 0.0282

GnomAD4 exome AF: 0.0298 AC: 42771 AN: 1433446 Hom.: 1130 Cov.: 31 AF XY: 0.0306 AC XY: 21839 AN XY: 712610

African (AFR) AF: 0.174 AC: 5704 AN: 32798

American (AMR) AF: 0.0164 AC: 704 AN: 42934

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 1811 AN: 25500

East Asian (EAS) AF: 0.00641 AC: 246 AN: 38380

South Asian (SAS) AF: 0.0641 AC: 5256 AN: 82038

European-Finnish (FIN) AF: 0.0210 AC: 1098 AN: 52332

Middle Eastern (MID) AF: 0.0481 AC: 272 AN: 5654

European-Non Finnish (NFE) AF: 0.0234 AC: 25589 AN: 1094988

Other (OTH) AF: 0.0355 AC: 2091 AN: 58822

GnomAD4 genome AF: 0.0866 AC: 9349 AN: 107944 Hom.: 560 Cov.: 28 AF XY: 0.0849 AC XY: 4561 AN XY: 53706

African (AFR) AF: 0.214 AC: 6545 AN: 30588

American (AMR) AF: 0.0374 AC: 384 AN: 10262

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 246 AN: 2454

East Asian (EAS) AF: 0.0106 AC: 39 AN: 3678

South Asian (SAS) AF: 0.0746 AC: 268 AN: 3594

European-Finnish (FIN) AF: 0.0264 AC: 222 AN: 8418

Middle Eastern (MID) AF: 0.108 AC: 20 AN: 186

European-Non Finnish (NFE) AF: 0.0323 AC: 1513 AN: 46826

Other (OTH) AF: 0.0795 AC: 112 AN: 1408

Alfa AF: 0.0358 Hom.: 937

Bravo AF: 0.0661

TwinsUK AF: 0.0267 AC: 99

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.148 AC: 653

ESP6500EA AF: 0.0253 AC: 218

ExAC AF: 0.0394 AC: 4781

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.85
DEOGEN2	Benign	0.090	.;.;T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.54	.;T;T;T;T;.
MetaRNN	Benign	0.0013	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;N;N;.;N;N
PhyloP100		0.78
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.29	T;T;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B
Vest4		0.044
MPC		0.24
ClinPred		0.00017	T
GERP RS		1.3
Varity_R		0.085
gMVP		0.28
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: rs17009792; hg19: chr2-74489323; COSMIC: COSV61026673; COSMIC: COSV61026673;