chr12-57429802-A-C

Position:

• chr12-57429802-A-C

Variant summary

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

The NM_001394031.1(R3HDM2):​c.-106+918T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 150,662 control chromosomes in the GnomAD database, including 3,026 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 (3026 hom., cov: 30)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.-106+918T>G		intron_variant		ENST00000402412.6	NP_001380960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM2	ENST00000402412.6	c.-106+918T>G		intron_variant		1	NM_001394031.1	ENSP00000385839	P1
R3HDM2	ENST00000347140.7	c.-106+918T>G		intron_variant		1		ENSP00000317903
R3HDM2	ENST00000448732.1	c.-36+918T>G		intron_variant		1		ENSP00000405777
R3HDM2	ENST00000634871.1	c.-106+918T>G		intron_variant		5		ENSP00000489424

Frequencies

GnomAD3 genomes AF: 0.185 AC: 27874 AN: 150548 Hom.: 3016 Cov.: 30

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.185 AC: 27895 AN: 150662 Hom.: 3026 Cov.: 30 AF XY: 0.181 AC XY: 13278 AN XY: 73396

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.0916

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.173

Alfa AF: 0.119 Hom.: 201

Bravo AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.59

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: rs7964492; hg19: chr12-57823585; COSMIC: COSV59005890; COSMIC: COSV59005890;