18-74292289-A-C

Position:

• chr18-74292289-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The variant allele was found at a frequency of 0.0145 in 152,294 control chromosomes in the GnomAD database, including 29 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 0.015 (29 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0145 (2212/152294) while in subpopulation SAS AF= 0.0442 (213/4824). AF 95% confidence interval is 0.0393. There are 29 homozygotes in gnomad4. There are 1108 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2199 AN: 152176 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0145 AC: 2212 AN: 152294 Hom.: 29 Cov.: 32 AF XY: 0.0149 AC XY: 1108 AN XY: 74480

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00545

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0114 Hom.: 0

Bravo AF: 0.0149

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77569097; hg19: chr18-71959524;