20-4800552-T-C

Variant names:

• chr20-4800552-T-C
• rs1535382
• NM_014737.3:c.59+420A>G

Variant summary

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

The NM_014737.3(RASSF2):​c.59+420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,958 control chromosomes in the GnomAD database, including 31,803 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 0.64 (31803 hom., cov: 31)
• Consequence: RASSF2 NM_014737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 4 publications found

Genes affected

RASSF2 (HGNC:9883): (Ras association domain family member 2) This gene encodes a protein that contains a Ras association domain. Similar to its cattle and sheep counterparts, this gene is located near the prion gene. Two alternatively spliced transcripts encoding the same isoform have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014737.3. 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
	RASSF2	NM_014737.3	MANE Select	c.59+420A>G		intron	N/A	NP_055552.1	P50749-1
	RASSF2	NM_170774.2		c.59+420A>G		intron	N/A	NP_739580.1	P50749-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF2	ENST00000379400.8	TSL:1 MANE Select	c.59+420A>G		intron	N/A	ENSP00000368710.3	P50749-1
	RASSF2	ENST00000379376.2	TSL:1	c.59+420A>G		intron	N/A	ENSP00000368684.2	P50749-1
	RASSF2	ENST00000872650.1		c.59+420A>G		intron	N/A	ENSP00000542709.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97411 AN: 151840 Hom.: 31768 Cov.: 31

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.642 AC: 97497 AN: 151958 Hom.: 31803 Cov.: 31 AF XY: 0.637 AC XY: 47325 AN XY: 74282

African (AFR) AF: 0.747 AC: 30996 AN: 41480

American (AMR) AF: 0.671 AC: 10245 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2173 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3235 AN: 5148

South Asian (SAS) AF: 0.481 AC: 2316 AN: 4814

European-Finnish (FIN) AF: 0.564 AC: 5951 AN: 10554

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40350 AN: 67916

Other (OTH) AF: 0.639 AC: 1349 AN: 2112

Alfa AF: 0.608 Hom.: 25163

Bravo AF: 0.659

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.60
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: rs1535382; hg19: chr20-4781198;