rs2117511

Positions:

• chr2-135705091-C-T

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2460-4342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,062 control chromosomes in the GnomAD database, including 42,193 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 0.71 (42193 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.2460-4342C>T		intron_variant		ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2460-4342C>T		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108564 AN: 151944 Hom.: 42185 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.714 AC: 108606 AN: 152062 Hom.: 42193 Cov.: 32 AF XY: 0.709 AC XY: 52740 AN XY: 74348

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.735

Alfa AF: 0.846 Hom.: 97091

Bravo AF: 0.689

Asia WGS AF: 0.590 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.65

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: rs2117511; hg19: chr2-136462661;