19-903241-A-C

Variant names:

• chr19-903241-A-C
• rs2046476
• NM_138774.4:c.72-1111T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138774.4. 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
	R3HDM4	NM_138774.4	MANE Select	c.72-1111T>G		intron	N/A	NP_620129.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM4	ENST00000361574.10	TSL:1 MANE Select	c.72-1111T>G		intron	N/A	ENSP00000355385.4	Q96D70
	R3HDM4	ENST00000861805.1		c.72-1111T>G		intron	N/A	ENSP00000531864.1
	R3HDM4	ENST00000934480.1		c.72-1111T>G		intron	N/A	ENSP00000604539.1

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

African (AFR) AF: 0.201 AC: 7608 AN: 37932

American (AMR) AF: 0.446 AC: 6511 AN: 14584

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1294 AN: 3294

East Asian (EAS) AF: 0.162 AC: 759 AN: 4674

South Asian (SAS) AF: 0.344 AC: 1515 AN: 4398

European-Finnish (FIN) AF: 0.372 AC: 3495 AN: 9394

Middle Eastern (MID) AF: 0.475 AC: 135 AN: 284

European-Non Finnish (NFE) AF: 0.406 AC: 26500 AN: 65328

Other (OTH) AF: 0.361 AC: 717 AN: 1984

Alfa AF: 0.240 Hom.: 571

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.79
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: rs2046476; hg19: chr19-903241;