3-50331566-G-A

Variant names:

• chr3-50331566-G-A
• rs55833676
• NM_007182.5:c.753C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_007182.5(RASSF1):​c.753C>T​(p.His251His) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 786011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007182.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF1	NM_007182.5	MANE Select	c.753C>T	p.His251His	synonymous	Exon 4 of 6	NP_009113.3
	RASSF1	NM_170714.2		c.765C>T	p.His255His	synonymous	Exon 4 of 6	NP_733832.1	Q9NS23-1
	RASSF1	NM_170713.3		c.543C>T	p.His181His	synonymous	Exon 3 of 5	NP_733831.1	Q9NS23-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF1	ENST00000359365.9	TSL:1 MANE Select	c.753C>T	p.His251His	synonymous	Exon 4 of 6	ENSP00000352323.4	Q9NS23-2
	RASSF1	ENST00000357043.6	TSL:1	c.765C>T	p.His255His	synonymous	Exon 4 of 6	ENSP00000349547.2	Q9NS23-1
	RASSF1	ENST00000327761.7	TSL:1	c.543C>T	p.His181His	synonymous	Exon 3 of 5	ENSP00000333327.3	Q9NS23-4

Frequencies

GnomAD3 genomes AF: 0.00937 AC: 1427 AN: 152232 Hom.: 26 Cov.: 33

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

GnomAD2 exomes AF: 0.00250 AC: 616 AN: 246082 AF XY: 0.00178

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 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.: 27 Cov.: 33 AF XY: 0.000822 AC XY: 583 AN XY: 708912

African (AFR) AF: 0.0377 AC: 1241 AN: 32954

American (AMR) AF: 0.000869 AC: 38 AN: 43704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25496

East Asian (EAS) AF: 0.00 AC: 0 AN: 39002

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52856

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.0000348 AC: 38 AN: 1091998

Other (OTH) AF: 0.00191 AC: 113 AN: 59104

GnomAD4 genome AF: 0.00939 AC: 1430 AN: 152350 Hom.: 26 Cov.: 33 AF XY: 0.00883 AC XY: 658 AN XY: 74492

African (AFR) AF: 0.0333 AC: 1386 AN: 41584

American (AMR) AF: 0.00209 AC: 32 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00424 Hom.: 9

Bravo AF: 0.0111

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.077
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs55833676; hg19: chr3-50368997;