4-73581793-A-G

Variant names:

• chr4-73581793-A-G
• rs1247671
• NM_177532.5:c.721+24T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177532.5(RASSF6):​c.721+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: RASSF6 NM_177532.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF6	NM_177532.5	c.721+24T>C		intron_variant	Intron 8 of 10	ENST00000307439.10	NP_803876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF6	ENST00000307439.10	c.721+24T>C		intron_variant	Intron 8 of 10	1	NM_177532.5	ENSP00000303877.5
RASSF6	ENST00000335049.5	c.685+24T>C		intron_variant	Intron 7 of 9	1		ENSP00000335582.5
RASSF6	ENST00000395777.6	c.619+24T>C		intron_variant	Intron 7 of 9	1		ENSP00000379123.2
RASSF6	ENST00000342081.7	c.817+24T>C		intron_variant	Intron 8 of 10	2		ENSP00000340578.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.79

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: rs1247671; hg19: chr4-74447510;