rs227450

Variant names:

• chr6-165066512-C-T
• rs227450
• ENST00000667740.1:n.270-9712C>T

Variant summary

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

The ENST00000667740.1(ENSG00000287877):​n.270-9712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 148,018 control chromosomes in the GnomAD database, including 33 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 (33 hom., cov: 32)
• Consequence: ENSG00000287877 ENST00000667740.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 1 publications found

Genes affected

ENSG00000287877 (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 afr. GnomAd4 allele frequency = 0.0126 (1862/148018) while in subpopulation AFR AF = 0.0437 (1742/39860). AF 95% confidence interval is 0.042. There are 33 homozygotes in GnomAd4. There are 916 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287877	ENST00000667740.1	n.270-9712C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1852 AN: 147910 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00378

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0199

Gnomad NFE AF: 0.000535

Gnomad OTH AF: 0.0103

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

GnomAD4 genome AF: 0.0126 AC: 1862 AN: 148018 Hom.: 33 Cov.: 32 AF XY: 0.0127 AC XY: 916 AN XY: 71906

African (AFR) AF: 0.0437 AC: 1742 AN: 39860

American (AMR) AF: 0.00377 AC: 56 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9604

Middle Eastern (MID) AF: 0.0213 AC: 6 AN: 282

European-Non Finnish (NFE) AF: 0.000535 AC: 36 AN: 67242

Other (OTH) AF: 0.0102 AC: 21 AN: 2060

Alfa AF: 0.0112 Hom.: 8

Bravo AF: 0.0137

Asia WGS AF: 0.00289 AC: 10 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	5.1
DANN	Benign	0.70
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs227450; hg19: chr6-165480001;