1-206524916-G-A

Position:

• chr1-206524916-G-A

Variant summary

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

The NM_182663.4(RASSF5):​c.458-13256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 151,092 control chromosomes in the GnomAD database, including 663 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 0.072 (663 hom., cov: 28)
• Consequence: RASSF5 NM_182663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

Genes affected

RASSF5 (HGNC:17609): (Ras association domain family member 5) This gene is a member of the Ras association domain family. It functions as a tumor suppressor, and is inactivated in a variety of cancers. The encoded protein localizes to centrosomes and microtubules, and associates with the GTP-activated forms of Ras, Rap1, and several other Ras-like small GTPases. The protein regulates lymphocyte adhesion and suppresses cell growth in response to activated Rap1 or Ras. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF5	NM_182663.4	c.458-13256G>A		intron_variant		ENST00000579436.7	NP_872604.1
RASSF5	NM_182664.4	c.458-13256G>A		intron_variant			NP_872605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF5	ENST00000579436.7	c.458-13256G>A		intron_variant		1	NM_182663.4	ENSP00000462099.1
RASSF5	ENST00000581503.6	c.458-13256G>A		intron_variant		1		ENSP00000464039.2
RASSF5	ENST00000580449.5	c.458-13256G>A		intron_variant		1		ENSP00000462544.1
RASSF5	ENST00000636182.1	c.157+6372G>A		intron_variant		5		ENSP00000489689.1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10866 AN: 150976 Hom.: 665 Cov.: 28

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0442

Gnomad EAS AF: 0.00407

Gnomad SAS AF: 0.0283

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0606

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

GnomAD4 genome AF: 0.0720 AC: 10875 AN: 151092 Hom.: 663 Cov.: 28 AF XY: 0.0698 AC XY: 5153 AN XY: 73818

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0442

Gnomad4 EAS AF: 0.00408

Gnomad4 SAS AF: 0.0287

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0585

Alfa AF: 0.0405 Hom.: 150

Bravo AF: 0.0765

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.53

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: rs11118968; hg19: chr1-206698249;