12-57273478-G-C

Variant names:

• chr12-57273478-G-C
• rs10783819
• NM_001394031.1:c.1345-3484C>G

Variant summary

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

The NM_001394031.1(R3HDM2):​c.1345-3484C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,012 control chromosomes in the GnomAD database, including 15,741 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 0.45 (15741 hom., cov: 31)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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]

ENSG00000258830 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.1345-3484C>G		intron_variant	Intron 14 of 23	ENST00000402412.6	NP_001380960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM2	ENST00000402412.6	c.1345-3484C>G		intron_variant	Intron 14 of 23	1	NM_001394031.1	ENSP00000385839.1
ENSG00000258830	ENST00000548184.1	n.*395-3484C>G		intron_variant	Intron 4 of 14	2		ENSP00000477227.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67878 AN: 151894 Hom.: 15722 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.447 AC: 67925 AN: 152012 Hom.: 15741 Cov.: 31 AF XY: 0.454 AC XY: 33712 AN XY: 74308

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.422

Alfa AF: 0.336 Hom.: 980

Bravo AF: 0.437

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.072
DANN	Benign	0.40

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: rs10783819; hg19: chr12-57667261;