chr22-32225482-G-A

Variant names:

• chr22-32225482-G-A
• rs2294207
• NM_014227.3:c.1449+173C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.93).
• 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 rank	MANE	Protein	UniProt
SLC5A4	NM_014227.3	c.1449+173C>T		intron_variant	Intron 12 of 14	ENST00000266086.6	NP_055042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A4	ENST00000266086.6	c.1449+173C>T		intron_variant	Intron 12 of 14	1	NM_014227.3	ENSP00000266086.3
SLC5A4-AS1	ENST00000434942.2	n.225-3608G>A		intron_variant	Intron 2 of 4	3
SLC5A4-AS1	ENST00000452181.2	n.274+18206G>A		intron_variant	Intron 2 of 4	5

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

African (AFR) AF: 0.183 AC: 7581 AN: 41458

American (AMR) AF: 0.158 AC: 2415 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.102 AC: 527 AN: 5182

South Asian (SAS) AF: 0.165 AC: 794 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2182 AN: 10584

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15543 AN: 67970

Other (OTH) AF: 0.186 AC: 393 AN: 2110

Alfa AF: 0.218 Hom.: 5663

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
PhyloP100		-0.030
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: rs2294207; hg19: chr22-32621469;