1-206554646-C-T

Variant names:

• chr1-206554646-C-T
• rs12569123
• NM_182663.4:c.579+16353C>T

Variant summary

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

The NM_182663.4(RASSF5):​c.579+16353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,076 control chromosomes in the GnomAD database, including 3,592 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 0.21 (3592 hom., cov: 32)
• Consequence: RASSF5 NM_182663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF5	NM_182663.4	c.579+16353C>T		intron_variant	Intron 2 of 5	ENST00000579436.7	NP_872604.1
RASSF5	NM_182664.4	c.579+16353C>T		intron_variant	Intron 2 of 4		NP_872605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF5	ENST00000579436.7	c.579+16353C>T		intron_variant	Intron 2 of 5	1	NM_182663.4	ENSP00000462099.1
RASSF5	ENST00000581503.6	c.579+16353C>T		intron_variant	Intron 2 of 3	1		ENSP00000464039.2
RASSF5	ENST00000580449.5	c.579+16353C>T		intron_variant	Intron 2 of 4	1		ENSP00000462544.1
RASSF5	ENST00000636182.1	c.279+16353C>T		intron_variant	Intron 2 of 5	5		ENSP00000489689.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32010 AN: 151956 Hom.: 3593 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.211 AC: 32013 AN: 152076 Hom.: 3592 Cov.: 32 AF XY: 0.214 AC XY: 15886 AN XY: 74348

African (AFR) AF: 0.133 AC: 5529 AN: 41484

American (AMR) AF: 0.260 AC: 3968 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1312 AN: 5182

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4812

European-Finnish (FIN) AF: 0.198 AC: 2099 AN: 10588

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15893 AN: 67962

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.213 Hom.: 475

Bravo AF: 0.211

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		-0.14

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: rs12569123; hg19: chr1-206727974;