20-44341158-A-G

Variant names:

• chr20-44341158-A-G
• rs3761184
• NM_178491.4:c.262-38A>G

Variant summary

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

The ENST00000217043.4(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 ENST00000217043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 14 publications found

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]

R3HDML-AS1 (HGNC:55830): (R3HDML antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000217043.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDML	NM_178491.4	MANE Select	c.262-38A>G		intron	N/A	NP_848586.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDML	ENST00000217043.4	TSL:1 MANE Select	c.262-38A>G		intron	N/A	ENSP00000217043.3
	R3HDML-AS1	ENST00000735551.1		n.601-2098T>C		intron	N/A

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

GnomAD2 exomes AF: 0.218 AC: 52111 AN: 239062 AF XY: 0.213

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 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

African (AFR) AF: 0.122 AC: 3916 AN: 32022

American (AMR) AF: 0.383 AC: 16283 AN: 42494

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 4906 AN: 24610

East Asian (EAS) AF: 0.387 AC: 15076 AN: 38940

South Asian (SAS) AF: 0.242 AC: 20066 AN: 82852

European-Finnish (FIN) AF: 0.122 AC: 6422 AN: 52786

Middle Eastern (MID) AF: 0.166 AC: 856 AN: 5154

European-Non Finnish (NFE) AF: 0.161 AC: 169051 AN: 1048814

Other (OTH) AF: 0.182 AC: 10454 AN: 57470

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

African (AFR) AF: 0.133 AC: 5522 AN: 41576

American (AMR) AF: 0.297 AC: 4531 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3472

East Asian (EAS) AF: 0.373 AC: 1920 AN: 5146

South Asian (SAS) AF: 0.261 AC: 1262 AN: 4828

European-Finnish (FIN) AF: 0.118 AC: 1253 AN: 10608

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11098 AN: 68012

Other (OTH) AF: 0.175 AC: 368 AN: 2104

Alfa AF: 0.156 Hom.: 1137

Bravo AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.71
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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