rs4954280

chr2-135663120-A-Gchr2-135663120-A-T

Variant summary

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

The NM_001378107.1(R3HDM1):c.2152+1727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 146,722 control chromosomes in the GnomAD database, including 22,063 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 (22063 hom., cov: 23)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LOC124907893 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.2152+1727A>G		intron_variant		ENST00000683871.1
LOC124907893	XR_007087245.1	n.1722A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2152+1727A>G		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 71451 AN: 146642 Hom.: 22016 Cov.: 23

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.488 AC: 71542 AN: 146722 Hom.: 22063 Cov.: 23 AF XY: 0.499 AC XY: 35590 AN XY: 71280

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.540

Alfa AF: 0.343 Hom.: 3045

Bravo AF: 0.524

Asia WGS AF: 0.780 AC: 2709 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.3
Dann	Benign	0.39

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: rs4954280; hg19: chr2-136420690;