rs984763

Positions:

• chr2-135587468-G-A

Variant summary

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

The NM_001378107.1(R3HDM1):​c.-249-15032G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 152,108 control chromosomes in the GnomAD database, including 912 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 0.093 (912 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.-249-15032G>A		intron_variant		ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.-249-15032G>A		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14165 AN: 151990 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.0617

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0932 AC: 14172 AN: 152108 Hom.: 912 Cov.: 32 AF XY: 0.0989 AC XY: 7352 AN XY: 74344

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0769 Hom.: 147

Bravo AF: 0.0970

Asia WGS AF: 0.245 AC: 849 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.60

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: rs984763; hg19: chr2-136345038;