rs149932910

Variant names:

• chr3-50337275-G-A
• rs149932910
• ENST00000327761.7:c.45C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-50337275-G-A
• chr3-50337275-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_170713.3(RASSF1):​c.45C>T​(p.Ser15Ser) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000839 in 1,613,142 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (1 hom.)
• Consequence: RASSF1 NM_170713.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.28
• Publications: 0 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]

RASSF1-AS1 (HGNC:49091): (RASSF1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 3-50337275-G-A is Benign according to our data. Variant chr3-50337275-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2653857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170713.3. 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.357+630C>T		intron	N/A	NP_009113.3
	RASSF1	NM_170713.3		c.45C>T	p.Ser15Ser	synonymous	Exon 1 of 5	NP_733831.1	Q9NS23-4
	RASSF1	NM_170714.2		c.369+630C>T		intron	N/A	NP_733832.1	Q9NS23-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF1	ENST00000327761.7	TSL:1	c.45C>T	p.Ser15Ser	synonymous	Exon 1 of 5	ENSP00000333327.3	Q9NS23-4
	RASSF1	ENST00000359365.9	TSL:1 MANE Select	c.357+630C>T		intron	N/A	ENSP00000352323.4	Q9NS23-2
	RASSF1	ENST00000357043.6	TSL:1	c.369+630C>T		intron	N/A	ENSP00000349547.2	Q9NS23-1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 465 AN: 152260 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00907

GnomAD2 exomes AF: 0.00108 AC: 266 AN: 247058 AF XY: 0.000945

Gnomad AFR exome AF: 0.00975

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000462

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000609 AC: 889 AN: 1460766 Hom.: 1 Cov.: 31 AF XY: 0.000615 AC XY: 447 AN XY: 726694

African (AFR) AF: 0.00843 AC: 282 AN: 33460

American (AMR) AF: 0.00161 AC: 72 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52734

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000392 AC: 436 AN: 1111708

Other (OTH) AF: 0.00144 AC: 87 AN: 60350

GnomAD4 genome AF: 0.00305 AC: 465 AN: 152376 Hom.: 2 Cov.: 33 AF XY: 0.00287 AC XY: 214 AN XY: 74518

African (AFR) AF: 0.00882 AC: 367 AN: 41592

American (AMR) AF: 0.00287 AC: 44 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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: 0.000514 AC: 35 AN: 68034

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00369

EpiCase AF: 0.000818

EpiControl AF: 0.000830

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		7.3
PromoterAI		0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=74/26	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: rs149932910; hg19: chr3-50374706;