rs2304368

Positions:

• chr2-135709989-C-A

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2564-70C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,436,632 control chromosomes in the GnomAD database, including 2,006 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 0.076 (932 hom., cov: 33)
  • Exomes 𝑓: 0.025 (1074 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.2564-70C>A		intron_variant		ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2564-70C>A		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11540 AN: 152068 Hom.: 928 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0647

GnomAD4 exome AF: 0.0254 AC: 32660 AN: 1284446 Hom.: 1074 AF XY: 0.0254 AC XY: 16236 AN XY: 638806

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0433

Gnomad4 ASJ exome AF: 0.0524

Gnomad4 EAS exome AF: 0.0522

Gnomad4 SAS exome AF: 0.0155

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome AF: 0.0760 AC: 11566 AN: 152186 Hom.: 932 Cov.: 33 AF XY: 0.0733 AC XY: 5452 AN XY: 74408

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.0148

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0650

Alfa AF: 0.0624 Hom.: 106

Bravo AF: 0.0848

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.33

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: rs2304368; hg19: chr2-136467559;