Variant chr3-50331566-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007182.5(RASSF1):c.753C>T(p.His251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,588,444 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 26 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 27 hom. )

Consequence

RASSF1
NM_007182.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0770

Variant links:

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]

RASSF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 3-50331566-G-A is Benign according to our data. Variant chr3-50331566-G-A is described in ClinVar as [Benign]. Clinvar id is 786011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-50331566-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.077 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00939 (1430/152350) while in subpopulation AFR AF= 0.0333 (1386/41584). AF 95% confidence interval is 0.0319. There are 26 homozygotes in gnomad4. There are 658 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF1	NM_007182.5 linkuse as main transcript	c.753C>T	p.His251=	synonymous_variant	4/6	ENST00000359365.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF1	ENST00000359365.9 linkuse as main transcript	c.753C>T	p.His251=	synonymous_variant	4/6	1	NM_007182.5	P1	Q9NS23-2

Frequencies

GnomAD3 genomes

AF:

0.00937

AC:

1427

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0334

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00250

AC:

616

AN:

246082

Hom.:

AF XY:

0.00178

AC XY:

237

AN XY:

133206

show subpopulations

Gnomad AFR exome

AF:

0.0358

Gnomad AMR exome

AF:

0.000856

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.000837

GnomAD4 exome

AF:

0.000999

AC:

1434

AN:

1436094

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

583

AN XY:

708912

show subpopulations

Gnomad4 AFR exome

AF:

0.0377

Gnomad4 AMR exome

AF:

0.000869

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000348

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

AF:

0.00939

AC:

1430

AN:

152350

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

658

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.4

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over