2-135666334-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.2152+4941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,036 control chromosomes in the GnomAD database, including 5,905 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 0.25 (5905 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.2152+4941C>T		intron_variant		ENST00000683871.1
LOC124907893	XR_007087245.1	n.4936C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2152+4941C>T		intron_variant			NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38189 AN: 151918 Hom.: 5886 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.252 AC: 38257 AN: 152036 Hom.: 5905 Cov.: 32 AF XY: 0.260 AC XY: 19332 AN XY: 74322

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.309

Alfa AF: 0.217 Hom.: 5311

Bravo AF: 0.269

Asia WGS AF: 0.485 AC: 1684 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	1.0
Dann	Benign	0.38

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: rs2289959; hg19: chr2-136423904;