rs2294208

Positions:

• chr22-32225632-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014227.3(SLC5A4):​c.1449+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,534,040 control chromosomes in the GnomAD database, including 166,117 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 0.51 (21069 hom., cov: 32)
  • Exomes 𝑓: 0.45 (145048 hom.)
• Consequence: SLC5A4 NM_014227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A4	NM_014227.3	c.1449+23G>A		intron_variant		ENST00000266086.6	NP_055042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A4	ENST00000266086.6	c.1449+23G>A		intron_variant		1	NM_014227.3	ENSP00000266086.3
SLC5A4-AS1	ENST00000434942.2	n.225-3458C>T		intron_variant		3
SLC5A4-AS1	ENST00000452181.2	n.274+18356C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76908 AN: 151834 Hom.: 21027 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.461

GnomAD3 exomes AF: 0.424 AC: 89678 AN: 211306 Hom.: 20528 AF XY: 0.426 AC XY: 49037 AN XY: 115150

Gnomad AFR exome AF: 0.718

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.401

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.462

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.451 AC: 623226 AN: 1382088 Hom.: 145048 Cov.: 22 AF XY: 0.449 AC XY: 308359 AN XY: 686826

Gnomad4 AFR exome AF: 0.720

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.507 AC: 77013 AN: 151952 Hom.: 21069 Cov.: 32 AF XY: 0.499 AC XY: 37039 AN XY: 74288

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.460

Alfa AF: 0.482 Hom.: 4277

Bravo AF: 0.512

Asia WGS AF: 0.344 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.066
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294208; hg19: chr22-32621619; COSMIC: COSV56669260;