rs1106766

Variant names:

• chr12-57415673-C-T
• rs1106766
• NM_001394031.1:c.-106+15047G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394031.1(R3HDM2):​c.-106+15047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,222 control chromosomes in the GnomAD database, including 3,126 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 (3126 hom., cov: 32)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 54 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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 rank	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.-106+15047G>A		intron_variant	Intron 1 of 23	ENST00000402412.6	NP_001380960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM2	ENST00000402412.6	c.-106+15047G>A		intron_variant	Intron 1 of 23	1	NM_001394031.1	ENSP00000385839.1
R3HDM2	ENST00000347140.7	c.-106+15047G>A		intron_variant	Intron 1 of 23	1		ENSP00000317903.6
R3HDM2	ENST00000448732.1	c.-36+15047G>A		intron_variant	Intron 1 of 1	1		ENSP00000405777.1
R3HDM2	ENST00000634871.1	c.-106+15047G>A		intron_variant	Intron 1 of 23	5		ENSP00000489424.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28404 AN: 151162 Hom.: 3115 Cov.: 32

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0581

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.188 AC: 28428 AN: 151222 Hom.: 3126 Cov.: 32 AF XY: 0.186 AC XY: 13719 AN XY: 73810

African (AFR) AF: 0.0971 AC: 4001 AN: 41210

American (AMR) AF: 0.280 AC: 4263 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3468

East Asian (EAS) AF: 0.0981 AC: 507 AN: 5170

South Asian (SAS) AF: 0.0939 AC: 449 AN: 4780

European-Finnish (FIN) AF: 0.236 AC: 2408 AN: 10198

Middle Eastern (MID) AF: 0.0556 AC: 16 AN: 288

European-Non Finnish (NFE) AF: 0.231 AC: 15673 AN: 67892

Other (OTH) AF: 0.174 AC: 365 AN: 2100

Alfa AF: 0.218 Hom.: 9648

Bravo AF: 0.195

Asia WGS AF: 0.114 AC: 397 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	3.4
DANN	Benign	0.37
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1106766; hg19: chr12-57809456;