12-64618200-G-A

Position:

• chr12-64618200-G-A

Variant summary

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

The NM_178169.4(RASSF3):​c.111+7457G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,764 control chromosomes in the GnomAD database, including 9,541 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 0.34 (9541 hom., cov: 32)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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]

RASSF3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF3	NM_178169.4	c.111+7457G>A		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+7457G>A		intron_variant		1	NM_178169.4	ENSP00000443021.1
RASSF3	ENST00000637125.1	c.295-66587G>A		intron_variant		5		ENSP00000490100.1
RASSF3	ENST00000283172.8	n.111+7457G>A		intron_variant		2		ENSP00000283172.4

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51320 AN: 151648 Hom.: 9533 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.338 AC: 51326 AN: 151764 Hom.: 9541 Cov.: 32 AF XY: 0.336 AC XY: 24868 AN XY: 74120

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.336

Alfa AF: 0.410 Hom.: 18775

Bravo AF: 0.332

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.69

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: rs7313765; hg19: chr12-65011980;