rs1247653

Variant names:

• chr4-73598585-T-C
• rs1247653
• NM_177532.5:c.144+55A>G

Variant summary

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

The NM_177532.5(RASSF6):​c.144+55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 824,142 control chromosomes in the GnomAD database, including 213 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 0.023 (148 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (65 hom.)
• Consequence: RASSF6 NM_177532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 1 publications found

Genes affected

RASSF6 (HGNC:20796): (Ras association domain family member 6) This gene encodes a member of the Ras-association domain family (RASSF). Members of this family form the core of a highly conserved tumor suppressor network, the Salvador-Warts-Hippo (SWH) pathway. The protein encoded by this gene is a Ras effector protein that induces apoptosis. A genomic region containing this gene has been linked to susceptibility to viral bronchiolitis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177532.5. 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
	RASSF6	NM_177532.5	MANE Select	c.144+55A>G		intron	N/A	NP_803876.1	Q6ZTQ3-2
	RASSF6	NM_201431.2		c.240+55A>G		intron	N/A	NP_958834.1	Q6ZTQ3-1
	RASSF6	NM_001270392.1		c.109-4992A>G		intron	N/A	NP_001257321.1	Q6ZTQ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF6	ENST00000307439.10	TSL:1 MANE Select	c.144+55A>G		intron	N/A	ENSP00000303877.5	Q6ZTQ3-2
	RASSF6	ENST00000335049.5	TSL:1	c.109-4992A>G		intron	N/A	ENSP00000335582.5	Q6ZTQ3-3
	RASSF6	ENST00000395777.6	TSL:1	c.144+55A>G		intron	N/A	ENSP00000379123.2	Q6ZTQ3-4

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3522 AN: 151778 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00231 AC: 1552 AN: 672246 Hom.: 65 AF XY: 0.00189 AC XY: 675 AN XY: 357450

African (AFR) AF: 0.0767 AC: 1182 AN: 15414

American (AMR) AF: 0.00418 AC: 101 AN: 24168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19764

East Asian (EAS) AF: 0.00 AC: 0 AN: 32350

South Asian (SAS) AF: 0.000155 AC: 9 AN: 57940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48194

Middle Eastern (MID) AF: 0.00473 AC: 20 AN: 4230

European-Non Finnish (NFE) AF: 0.0000825 AC: 36 AN: 436588

Other (OTH) AF: 0.00607 AC: 204 AN: 33598

GnomAD4 genome AF: 0.0232 AC: 3519 AN: 151896 Hom.: 148 Cov.: 33 AF XY: 0.0227 AC XY: 1685 AN XY: 74262

African (AFR) AF: 0.0798 AC: 3304 AN: 41412

American (AMR) AF: 0.0103 AC: 157 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67900

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.00461 Hom.: 3

Bravo AF: 0.0266

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.32
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1247653; hg19: chr4-74464302;