12-57416471-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.-106+14249A>G		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+14249A>G		intron_variant	Intron 1 of 23	1	NM_001394031.1	ENSP00000385839.1
R3HDM2	ENST00000347140.7	c.-106+14249A>G		intron_variant	Intron 1 of 23	1		ENSP00000317903.6
R3HDM2	ENST00000448732.1	c.-36+14249A>G		intron_variant	Intron 1 of 1	1		ENSP00000405777.1
R3HDM2	ENST00000634871.1	c.-106+14249A>G		intron_variant	Intron 1 of 23	5		ENSP00000489424.1

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

GnomAD3 exomes AF: 0.375 AC: 3 AN: 8 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 2

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

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.413

Alfa AF: 0.463 Hom.: 6633

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs537482; hg19: chr12-57810254;