rs11172147

Positions:

• chr12-57302894-G-A

Variant summary

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

The NM_001394031.1(R3HDM2):​c.207+282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,040 control chromosomes in the GnomAD database, including 3,111 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 0.19 (3111 hom., cov: 31)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

Genes affected

R3HDM2 (HGNC:29167): (R3H domain containing 2) Enables RNA binding activity. Predicted to be located in nucleus. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.207+282C>T		intron_variant		ENST00000402412.6	NP_001380960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM2	ENST00000402412.6	c.207+282C>T		intron_variant		1	NM_001394031.1	ENSP00000385839.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28327 AN: 151924 Hom.: 3101 Cov.: 31

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.0930

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.186 AC: 28348 AN: 152040 Hom.: 3111 Cov.: 31 AF XY: 0.184 AC XY: 13684 AN XY: 74324

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0980

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.174

Alfa AF: 0.215 Hom.: 4958

Bravo AF: 0.194

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.66

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: rs11172147; hg19: chr12-57696677;