12-64622520-A-G

Position:

• chr12-64622520-A-G

Variant summary

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

The NM_178169.4(RASSF3):​c.111+11777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 530,676 control chromosomes in the GnomAD database, including 890 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 0.053 (725 hom., cov: 30)
  • Exomes 𝑓: 0.0066 (165 hom.)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

Genes affected

RASSF3 (HGNC:14271): (Ras association domain family member 3) The RAS oncogene (MIM 190020) is mutated in nearly one-third of all human cancers. Members of the RAS superfamily are plasma membrane GTP-binding proteins that modulate intracellular signal transduction pathways. A subfamily of RAS effectors, including RASSF3, share a RAS association (RA) domain.[supplied by OMIM, Jul 2003]

MIR548C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF3	NM_178169.4	c.111+11777A>G		intron_variant		ENST00000542104.6	NP_835463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF3	ENST00000542104.6	c.111+11777A>G		intron_variant		1	NM_178169.4	ENSP00000443021.1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7986 AN: 151900 Hom.: 723 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0141 AC: 3483 AN: 246442 Hom.: 293 AF XY: 0.0100 AC XY: 1338 AN XY: 133692

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.00974

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.000918

Gnomad OTH exome AF: 0.00776

GnomAD4 exome AF: 0.00664 AC: 2516 AN: 378658 Hom.: 165 Cov.: 0 AF XY: 0.00512 AC XY: 1105 AN XY: 215824

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000391

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.000590

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0526 AC: 7996 AN: 152018 Hom.: 725 Cov.: 30 AF XY: 0.0502 AC XY: 3730 AN XY: 74356

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000751

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0143 Hom.: 210

Bravo AF: 0.0611

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.63

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: rs17120527; hg19: chr12-65016300;