rs4954265

chr2-135566655-A-G

Variant summary

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

The NM_001378107.1(R3HDM1):c.-250+35022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 749,052 control chromosomes in the GnomAD database, including 13,156 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 0.26 (8817 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4339 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.-250+35022A>G		intron_variant		ENST00000683871.1
R3HDM1	NM_001282799.2	c.-250+35022A>G		intron_variant
R3HDM1	NM_001354200.2	c.-250+35022A>G		intron_variant
R3HDM1	NM_015361.4	c.-250+35022A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.-250+35022A>G		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38907 AN: 151958 Hom.: 8788 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.0789 AC: 47125 AN: 596976 Hom.: 4339 Cov.: 8 AF XY: 0.0788 AC XY: 22024 AN XY: 279482

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.212

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.0817

Gnomad4 NFE exome AF: 0.0597

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.256 AC: 38987 AN: 152076 Hom.: 8817 Cov.: 32 AF XY: 0.257 AC XY: 19116 AN XY: 74356

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0831

Gnomad4 OTH AF: 0.227

Alfa AF: 0.122 Hom.: 4169

Bravo AF: 0.281

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	12
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4954265; hg19: chr2-136324225;