rs313528

Positions:

• chr2-135688299-G-A
• chr2-135688299-G-C
• chr2-135688299-G-T

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2459+7975G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,040 control chromosomes in the GnomAD database, including 23,096 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 0.49 (23096 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.2459+7975G>A		intron_variant		ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2459+7975G>A		intron_variant			NM_001378107.1	ENSP00000506980	A1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74648 AN: 151920 Hom.: 23037 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.492 AC: 74771 AN: 152040 Hom.: 23096 Cov.: 32 AF XY: 0.503 AC XY: 37368 AN XY: 74312

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.538

Alfa AF: 0.329 Hom.: 5386

Bravo AF: 0.524

Asia WGS AF: 0.780 AC: 2712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.70

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: rs313528; hg19: chr2-136445869;