20-44341158-A-G

Position:

• chr20-44341158-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178491.4(R3HDML):​c.262-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,537,372 control chromosomes in the GnomAD database, including 27,719 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 0.18 (2765 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24954 hom.)
• Consequence: R3HDML NM_178491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

Genes affected

R3HDML (HGNC:16249): (R3H domain containing like) Predicted to enable peptidase inhibitor activity. Predicted to be involved in negative regulation of peptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDML	NM_178491.4	c.262-38A>G		intron_variant		ENST00000217043.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDML	ENST00000217043.4	c.262-38A>G		intron_variant		1	NM_178491.4	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26830 AN: 152112 Hom.: 2746 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.170

GnomAD3 exomes AF: 0.218 AC: 52111 AN: 239062 Hom.: 7002 AF XY: 0.213 AC XY: 27552 AN XY: 129222

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.380

Gnomad SAS exome AF: 0.249

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.202

GnomAD4 exome AF: 0.178 AC: 247030 AN: 1385142 Hom.: 24954 Cov.: 21 AF XY: 0.180 AC XY: 123735 AN XY: 688460

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.387

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.177 AC: 26878 AN: 152230 Hom.: 2765 Cov.: 33 AF XY: 0.180 AC XY: 13383 AN XY: 74420

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.175

Alfa AF: 0.155 Hom.: 970

Bravo AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3761184; hg19: chr20-42969798; COSMIC: COSV53838095; COSMIC: COSV53838095;