rs2294207

Positions:

• chr22-32225482-G-A

Variant summary

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

The NM_014227.3(SLC5A4):​c.1449+173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,062 control chromosomes in the GnomAD database, including 3,148 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 0.20 (3148 hom., cov: 33)
• Consequence: SLC5A4 NM_014227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A4	NM_014227.3	c.1449+173C>T		intron_variant		ENST00000266086.6	NP_055042.1
SLC5A4-AS1	NR_149072.1	n.274+18206G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A4	ENST00000266086.6	c.1449+173C>T		intron_variant		1	NM_014227.3	ENSP00000266086	P1
SLC5A4-AS1	ENST00000452181.2	n.274+18206G>A		intron_variant, non_coding_transcript_variant		5
SLC5A4-AS1	ENST00000434942.2	n.225-3608G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30513 AN: 151944 Hom.: 3148 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.201 AC: 30531 AN: 152062 Hom.: 3148 Cov.: 33 AF XY: 0.199 AC XY: 14811 AN XY: 74326

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.186

Alfa AF: 0.223 Hom.: 3887

Bravo AF: 0.195

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.69

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: rs2294207; hg19: chr22-32621469;