rs4251416

Variant names:

• chr17-30238543-A-G
• rs4251416
• ENST00000577420.2:n.2A>G

Variant summary

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

The ENST00000577420.2(ENSG00000266120):​n.2A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 151,924 control chromosomes in the GnomAD database, including 21 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 0.013 (21 hom., cov: 32)
• Consequence: ENSG00000266120 ENST00000577420.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 0 publications found

Genes affected

ENSG00000266120 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0134 (2035/151924) while in subpopulation NFE AF = 0.0229 (1554/67910). AF 95% confidence interval is 0.0219. There are 21 homozygotes in GnomAd4. There are 933 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371720	XR_001752824.2	n.634A>G		non_coding_transcript_exon_variant	Exon 3 of 4
LOC105371720	XR_007065695.1	n.498A>G		non_coding_transcript_exon_variant	Exon 2 of 3
LOC105371720	XR_007065696.1	n.498A>G		non_coding_transcript_exon_variant	Exon 2 of 3
LOC105371720	XR_007065698.1	n.498A>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000266120	ENST00000577420.2	n.2A>G		non_coding_transcript_exon_variant	Exon 1 of 3	3
ENSG00000266120	ENST00000724731.1	n.463A>G		non_coding_transcript_exon_variant	Exon 3 of 5
ENSG00000266120	ENST00000724730.1	n.-1A>G		upstream_gene_variant
ENSG00000266120	ENST00000724732.1	n.-88A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2035 AN: 151806 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00375

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00649

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00500

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0134 AC: 2035 AN: 151924 Hom.: 21 Cov.: 32 AF XY: 0.0126 AC XY: 933 AN XY: 74276

African (AFR) AF: 0.00374 AC: 155 AN: 41440

American (AMR) AF: 0.00648 AC: 99 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00501 AC: 24 AN: 4792

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0229 AC: 1554 AN: 67910

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.0197 Hom.: 3

Bravo AF: 0.0126

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.90
DANN	Benign	0.26
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs4251416; hg19: chr17-28565561; COSMIC: COSV55566301;