20-44346383-G-C

Position:

• chr20-44346383-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDML	NM_178491.4	c.629+1005G>C		intron_variant		ENST00000217043.4	NP_848586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDML	ENST00000217043.4	c.629+1005G>C		intron_variant		1	NM_178491.4	ENSP00000217043.3

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

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.209

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs4810424; hg19: chr20-42975023;