rs5998391

Variant names:

• chr22-32293653-C-G
• rs5998391
• ENST00000701275.2:n.403-27301G>C

Variant summary

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

The ENST00000701275.2(ENSG00000289873):​n.403-27301G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,564 control chromosomes in the GnomAD database, including 17,455 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 0.48 (17455 hom., cov: 31)
• Consequence: ENSG00000289873 ENST00000701275.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 0 publications found

Genes affected

ENSG00000289873 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A4	XM_017028920.2	c.108-27301G>C		intron_variant	Intron 2 of 16		XP_016884409.1
SLC5A4	XM_006724308.4	c.-3-39440G>C		intron_variant	Intron 2 of 15		XP_006724371.1
SLC5A4	XM_011530342.3	c.-121-27301G>C		intron_variant	Intron 2 of 16		XP_011528644.1
SLC5A4	XM_011530343.3	c.-3-39440G>C		intron_variant	Intron 1 of 14		XP_011528645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289873	ENST00000701275.2	n.403-27301G>C		intron_variant	Intron 2 of 2
ENSG00000289873	ENST00000701728.2	n.233-27301G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72456 AN: 151444 Hom.: 17437 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.478 AC: 72506 AN: 151564 Hom.: 17455 Cov.: 31 AF XY: 0.481 AC XY: 35591 AN XY: 74024

African (AFR) AF: 0.459 AC: 18971 AN: 41328

American (AMR) AF: 0.514 AC: 7837 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1409 AN: 3464

East Asian (EAS) AF: 0.368 AC: 1896 AN: 5154

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4824

European-Finnish (FIN) AF: 0.566 AC: 5916 AN: 10446

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32909 AN: 67804

Other (OTH) AF: 0.439 AC: 925 AN: 2108

Alfa AF: 0.489 Hom.: 2208

Bravo AF: 0.473

Asia WGS AF: 0.410 AC: 1415 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.6
DANN	Benign	0.89
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5998391; hg19: chr22-32689640;