12-57398797-C-T

Position:

• chr12-57398797-C-T

Variant summary

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

The NM_001394031.1(R3HDM2):​c.-105-2979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,144 control chromosomes in the GnomAD database, including 3,139 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 (3139 hom., cov: 32)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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 = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM2	NM_001394031.1	c.-105-2979G>A		intron_variant		ENST00000402412.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM2	ENST00000402412.6	c.-105-2979G>A		intron_variant		1	NM_001394031.1	P1
R3HDM2	ENST00000347140.7	c.-105-2979G>A		intron_variant		1
R3HDM2	ENST00000448732.1	c.-36+31923G>A		intron_variant		1
R3HDM2	ENST00000634871.1	c.-105-2979G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28427 AN: 152026 Hom.: 3128 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.187 AC: 28451 AN: 152144 Hom.: 3139 Cov.: 32 AF XY: 0.185 AC XY: 13737 AN XY: 74380

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.174

Alfa AF: 0.219 Hom.: 1574

Bravo AF: 0.194

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.73

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: rs11613352; hg19: chr12-57792580;