18-74292257-G-A

Variant names:

• chr18-74292257-G-A
• rs76631379
• ENST00000660707.2:n.12G>A

Variant summary

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

The ENST00000660707.2(ENSG00000286529):​n.12G>A 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 0.0191 in 152,340 control chromosomes in the GnomAD database, including 48 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 0.019 (48 hom., cov: 33)
• Consequence: ENSG00000286529 ENST00000660707.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 1 publications found

Genes affected

ENSG00000286529 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0191 (2917/152340) while in subpopulation NFE AF = 0.0312 (2124/68026). AF 95% confidence interval is 0.0301. There are 48 homozygotes in GnomAd4. There are 1360 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000660707.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286529	ENST00000660707.2		n.12G>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000286529	ENST00000849951.1		n.45G>A		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000286529	ENST00000849952.1		n.38G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2919 AN: 152222 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.00605

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0191 AC: 2917 AN: 152340 Hom.: 48 Cov.: 33 AF XY: 0.0183 AC XY: 1360 AN XY: 74490

African (AFR) AF: 0.00604 AC: 251 AN: 41578

American (AMR) AF: 0.0187 AC: 286 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4826

European-Finnish (FIN) AF: 0.0135 AC: 144 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0312 AC: 2124 AN: 68026

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.00357 Hom.: 1

Bravo AF: 0.0187

Asia WGS AF: 0.00751 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		-2.1
PromoterAI		0.15	Neutral

Splicing

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

Other links and lift over

dbSNP: rs76631379; hg19: chr18-71959492;