rs5998330

Positions:

• chr22-32238717-T-G

Variant summary

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

The NM_014227.3(SLC5A4):​c.583+268A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,052 control chromosomes in the GnomAD database, including 15,738 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 0.44 (15738 hom., cov: 31)
• Consequence: SLC5A4 NM_014227.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A4	NM_014227.3	c.583+268A>C		intron_variant		ENST00000266086.6	NP_055042.1
SLC5A4-AS1	NR_149072.1	n.275-29571T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A4	ENST00000266086.6	c.583+268A>C		intron_variant		1	NM_014227.3	ENSP00000266086	P1
SLC5A4-AS1	ENST00000452181.2	n.275-29571T>G		intron_variant, non_coding_transcript_variant		5
SLC5A4-AS1	ENST00000434942.2	n.507+9345T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67396 AN: 151934 Hom.: 15716 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.444 AC: 67469 AN: 152052 Hom.: 15738 Cov.: 31 AF XY: 0.435 AC XY: 32310 AN XY: 74330

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.403

Alfa AF: 0.445 Hom.: 3805

Bravo AF: 0.445

Asia WGS AF: 0.253 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs5998330; hg19: chr22-32634704;