rs2046476

chr19-903241-A-Cchr19-903241-A-T

Variant summary

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

The NM_138774.4(R3HDM4):c.72-1111T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 142,742 control chromosomes in the GnomAD database, including 8,742 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 0.34 (8742 hom., cov: 25)
• Consequence: R3HDM4 NM_138774.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790

Genes affected

R3HDM4 (HGNC:28270): (R3H domain containing 4) Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM4	NM_138774.4	c.72-1111T>G		intron_variant		ENST00000361574.10
R3HDM4	XM_011528416.3	c.72-1111T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM4	ENST00000361574.10	c.72-1111T>G		intron_variant		1	NM_138774.4	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 48889 AN: 142648 Hom.: 8736 Cov.: 25

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.343 AC: 48919 AN: 142742 Hom.: 8742 Cov.: 25 AF XY: 0.342 AC XY: 23722 AN XY: 69302

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.361

Alfa AF: 0.240 Hom.: 571

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.32

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: rs2046476; hg19: chr19-903241;