chr12-57416471-T-C

Variant names:

• chr12-57416471-T-C
• rs537482
• NM_001394031.1:c.-106+14249A>G

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+14249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,964 control chromosomes in the GnomAD database, including 15,129 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 0.44 (15129 hom., cov: 31)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394031.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	NM_001394031.1	MANE Select	c.-106+14249A>G		intron	N/A	NP_001380960.1	B5MCU0
	R3HDM2	NM_001351204.2		c.-106+14249A>G		intron	N/A	NP_001338133.1
	R3HDM2	NM_001351207.2		c.-106+6388A>G		intron	N/A	NP_001338136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	ENST00000402412.6	TSL:1 MANE Select	c.-106+14249A>G		intron	N/A	ENSP00000385839.1	B5MCU0
	R3HDM2	ENST00000347140.7	TSL:1	c.-106+14249A>G		intron	N/A	ENSP00000317903.6	Q9Y2K5-1
	R3HDM2	ENST00000448732.1	TSL:1	c.-36+14249A>G		intron	N/A	ENSP00000405777.1	C9J7N6

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66056 AN: 151846 Hom.: 15106 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.375 AC: 3 AN: 8 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.750

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

GnomAD4 genome AF: 0.435 AC: 66109 AN: 151964 Hom.: 15129 Cov.: 31 AF XY: 0.442 AC XY: 32818 AN XY: 74270

African (AFR) AF: 0.307 AC: 12704 AN: 41420

American (AMR) AF: 0.507 AC: 7734 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2324 AN: 5170

South Asian (SAS) AF: 0.521 AC: 2510 AN: 4822

European-Finnish (FIN) AF: 0.581 AC: 6120 AN: 10540

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32185 AN: 67958

Other (OTH) AF: 0.413 AC: 872 AN: 2112

Alfa AF: 0.458 Hom.: 7762

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs537482; hg19: chr12-57810254;