chr8-2804227-C-G

Variant names:

• chr8-2804227-C-G
• rs1454974
• ENST00000520024.1:n.177-359C>G

Variant summary

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

The ENST00000520024.1(ENSG00000253853):​n.177-359C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 151,962 control chromosomes in the GnomAD database, including 23 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 0.012 (23 hom., cov: 33)
• Consequence: ENSG00000253853 ENST00000520024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947
• Publications: 0 publications found

Genes affected

ENSG00000253853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377785	NR_168441.1	n.539-359C>G		intron_variant	Intron 1 of 11
LOC105377785	NR_168442.1	n.539-359C>G		intron_variant	Intron 1 of 14
LOC105377785	NR_168443.1	n.539-359C>G		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253853	ENST00000520024.1	n.177-359C>G		intron_variant	Intron 1 of 4	3
ENSG00000253853	ENST00000654515.1	n.532-359C>G		intron_variant	Intron 1 of 5
ENSG00000253853	ENST00000662575.1	n.82-359C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1883 AN: 151844 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00378

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00788

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.00570

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0124 AC: 1889 AN: 151962 Hom.: 23 Cov.: 33 AF XY: 0.0127 AC XY: 941 AN XY: 74258

African (AFR) AF: 0.00376 AC: 156 AN: 41442

American (AMR) AF: 0.00787 AC: 120 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.0659 AC: 340 AN: 5156

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4820

European-Finnish (FIN) AF: 0.00570 AC: 60 AN: 10530

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0136 AC: 926 AN: 67976

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.0104 Hom.: 2

Bravo AF: 0.0122

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.1
DANN	Benign	0.53
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1454974; hg19: chr8-2661745;