rs8137034

Variant names:

• chr22-32226552-A-G
• rs8137034
• NM_014227.3:c.1281-729T>C

Variant summary

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

The NM_014227.3(SLC5A4):​c.1281-729T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,164 control chromosomes in the GnomAD database, including 3,320 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 0.21 (3320 hom., cov: 33)
• Consequence: SLC5A4 NM_014227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 2 publications found

Genes affected

SLC5A4 (HGNC:11039): (solute carrier family 5 member 4) Predicted to enable glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in sodium ion transport. Predicted to act upstream of or within proton transmembrane transport. Predicted to be active in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A4-AS1 (HGNC:53163): (SLC5A4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A4	NM_014227.3	c.1281-729T>C		intron_variant	Intron 11 of 14	ENST00000266086.6	NP_055042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A4	ENST00000266086.6	c.1281-729T>C		intron_variant	Intron 11 of 14	1	NM_014227.3	ENSP00000266086.3
SLC5A4-AS1	ENST00000434942.2	n.225-2538A>G		intron_variant	Intron 2 of 4	3
SLC5A4-AS1	ENST00000452181.2	n.274+19276A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31327 AN: 152046 Hom.: 3320 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.206 AC: 31345 AN: 152164 Hom.: 3320 Cov.: 33 AF XY: 0.204 AC XY: 15197 AN XY: 74396

African (AFR) AF: 0.195 AC: 8094 AN: 41526

American (AMR) AF: 0.159 AC: 2433 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3468

East Asian (EAS) AF: 0.106 AC: 547 AN: 5180

South Asian (SAS) AF: 0.172 AC: 832 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2175 AN: 10592

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15762 AN: 67974

Other (OTH) AF: 0.191 AC: 402 AN: 2110

Alfa AF: 0.219 Hom.: 1473

Bravo AF: 0.200

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.66
PhyloP100		-0.46
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: rs8137034; hg19: chr22-32622539; COSMIC: COSV107237855;