rs2236947

Positions:

• chr3-50334001-C-A
• chr3-50334001-C-G

Variant summary

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

The NM_007182.5(RASSF1):​c.358-1847G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,014 control chromosomes in the GnomAD database, including 12,443 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 0.39 (12443 hom., cov: 32)
• Consequence: RASSF1 NM_007182.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884

Genes affected

RASSF1 (HGNC:9882): (Ras association domain family member 1) This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF1	NM_007182.5	c.358-1847G>T		intron_variant		ENST00000359365.9	NP_009113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF1	ENST00000359365.9	c.358-1847G>T		intron_variant		1	NM_007182.5	ENSP00000352323	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59121 AN: 151896 Hom.: 12439 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.389 AC: 59130 AN: 152014 Hom.: 12443 Cov.: 32 AF XY: 0.381 AC XY: 28280 AN XY: 74288

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.421

Alfa AF: 0.437 Hom.: 13345

Bravo AF: 0.384

Asia WGS AF: 0.221 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.61
DANN	Benign	0.68

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: rs2236947; hg19: chr3-50371432;