rs2304367

chr2-135709594-C-Achr2-135709594-C-Gchr2-135709594-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.2563+58C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,586,016 control chromosomes in the GnomAD database, including 780,208 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 0.97 (71883 hom., cov: 31)
  • Exomes 𝑓: 0.99 (708325 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.2563+58C>A		intron_variant		ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2563+58C>A		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147720 AN: 152184 Hom.: 71832 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.966

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.979

GnomAD4 exome AF: 0.994 AC: 1424908 AN: 1433714 Hom.: 708325 AF XY: 0.993 AC XY: 708128 AN XY: 712916

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.994

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.975

Gnomad4 SAS exome AF: 0.969

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.971 AC: 147830 AN: 152302 Hom.: 71883 Cov.: 31 AF XY: 0.970 AC XY: 72246 AN XY: 74478

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.966

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.980

Alfa AF: 0.976 Hom.: 11072

Bravo AF: 0.967

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.7
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: rs2304367; hg19: chr2-136467164;