chr5-128046610-C-T

Variant names:

• chr5-128046610-C-T
• rs146579248
• ENST00000499346.8:n.471+14534G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000499346.8(SLC12A2-DT):​n.471+14534G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 152,302 control chromosomes in the GnomAD database, including 51 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 0.021 (51 hom., cov: 33)
• Consequence: SLC12A2-DT ENST00000499346.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 6 publications found

Genes affected

SLC12A2-DT (HGNC:49565): (SLC12A2 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0212 (3228/152302) while in subpopulation NFE AF = 0.03 (2041/68012). AF 95% confidence interval is 0.0289. There are 51 homozygotes in GnomAd4. There are 1547 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A2-DT	NR_015360.2	n.307+14534G>A		intron_variant	Intron 2 of 2
SLC12A2-DT	NR_152798.1	n.542+14534G>A		intron_variant	Intron 2 of 2
SLC12A2-DT	NR_152800.1	n.542+14534G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A2-DT	ENST00000499346.8	n.471+14534G>A		intron_variant	Intron 2 of 3	1
SLC12A2-DT	ENST00000501702.8	n.526+14534G>A		intron_variant	Intron 2 of 2	1
SLC12A2-DT	ENST00000514409.7	n.246+14534G>A		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3230 AN: 152184 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0224

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

GnomAD4 genome AF: 0.0212 AC: 3228 AN: 152302 Hom.: 51 Cov.: 33 AF XY: 0.0208 AC XY: 1547 AN XY: 74484

African (AFR) AF: 0.00486 AC: 202 AN: 41568

American (AMR) AF: 0.0157 AC: 240 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5180

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4826

European-Finnish (FIN) AF: 0.0155 AC: 165 AN: 10624

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2041 AN: 68012

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.0175 Hom.: 9

Bravo AF: 0.0202

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.21
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs146579248; hg19: chr5-127382302;