20-44346383-G-C

Variant names:

• chr20-44346383-G-C
• rs4810424
• NM_178491.4:c.629+1005G>C

Variant summary

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

The NM_178491.4(R3HDML):​c.629+1005G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,176 control chromosomes in the GnomAD database, including 3,466 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 0.19 (3466 hom., cov: 33)
• Consequence: R3HDML NM_178491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 20 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178491.4. 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
	R3HDML	NM_178491.4	MANE Select	c.629+1005G>C		intron	N/A	NP_848586.1	Q9H3Y0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDML	ENST00000217043.4	TSL:1 MANE Select	c.629+1005G>C		intron	N/A	ENSP00000217043.3	Q9H3Y0
	R3HDML-AS1	ENST00000735551.1		n.600+4237C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28290 AN: 152058 Hom.: 3449 Cov.: 33

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.186 AC: 28332 AN: 152176 Hom.: 3466 Cov.: 33 AF XY: 0.195 AC XY: 14483 AN XY: 74394

African (AFR) AF: 0.0929 AC: 3859 AN: 41548

American (AMR) AF: 0.373 AC: 5695 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2277 AN: 5162

South Asian (SAS) AF: 0.304 AC: 1465 AN: 4826

European-Finnish (FIN) AF: 0.211 AC: 2233 AN: 10594

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11356 AN: 67994

Other (OTH) AF: 0.209 AC: 440 AN: 2106

Alfa AF: 0.0808 Hom.: 112

Bravo AF: 0.197

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.78
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4810424; hg19: chr20-42975023;