12-64641079-C-T

Variant names:

• chr12-64641079-C-T
• rs2682724
• NM_178169.4:c.111+30336C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178169.4(RASSF3):​c.111+30336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,884 control chromosomes in the GnomAD database, including 23,426 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 0.55 (23426 hom., cov: 31)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF3	NM_178169.4	c.111+30336C>T		intron_variant	Intron 1 of 4	ENST00000542104.6	NP_835463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF3	ENST00000542104.6	c.111+30336C>T		intron_variant	Intron 1 of 4	1	NM_178169.4	ENSP00000443021.1
RASSF3	ENST00000637125.1	c.295-43708C>T		intron_variant	Intron 2 of 5	5		ENSP00000490100.1
RASSF3	ENST00000283172.9	n.111+30336C>T		intron_variant	Intron 1 of 3	2		ENSP00000283172.4

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83836 AN: 151766 Hom.: 23417 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.552 AC: 83869 AN: 151884 Hom.: 23426 Cov.: 31 AF XY: 0.544 AC XY: 40404 AN XY: 74216

African (AFR) AF: 0.585 AC: 24248 AN: 41418

American (AMR) AF: 0.463 AC: 7063 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1921 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2613 AN: 5156

South Asian (SAS) AF: 0.519 AC: 2500 AN: 4814

European-Finnish (FIN) AF: 0.484 AC: 5089 AN: 10524

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38591 AN: 67936

Other (OTH) AF: 0.565 AC: 1188 AN: 2102

Alfa AF: 0.556 Hom.: 13496

Bravo AF: 0.552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2682724; hg19: chr12-65034859;