rs1247671

Positions:

• chr4-73581793-A-C
• chr4-73581793-A-G
• chr4-73581793-A-T

Variant summary

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

The NM_177532.5(RASSF6):​c.721+24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,549,720 control chromosomes in the GnomAD database, including 446,088 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 0.75 (42654 hom., cov: 32)
  • Exomes 𝑓: 0.76 (403434 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF6	NM_177532.5	c.721+24T>G		intron_variant		ENST00000307439.10	NP_803876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF6	ENST00000307439.10	c.721+24T>G		intron_variant		1	NM_177532.5	ENSP00000303877.5
RASSF6	ENST00000335049.5	c.685+24T>G		intron_variant		1		ENSP00000335582.5
RASSF6	ENST00000395777.6	c.619+24T>G		intron_variant		1		ENSP00000379123.2
RASSF6	ENST00000342081.7	c.817+24T>G		intron_variant		2		ENSP00000340578.3

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113567 AN: 151900 Hom.: 42639 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.725

GnomAD3 exomes AF: 0.757 AC: 188920 AN: 249680 Hom.: 72166 AF XY: 0.764 AC XY: 103065 AN XY: 134958

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.614

Gnomad ASJ exome AF: 0.722

Gnomad EAS exome AF: 0.900

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.760

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.758 AC: 1059508 AN: 1397702 Hom.: 403434 Cov.: 22 AF XY: 0.761 AC XY: 531986 AN XY: 698956

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.880

Gnomad4 SAS exome AF: 0.816

Gnomad4 FIN exome AF: 0.787

Gnomad4 NFE exome AF: 0.756

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.747 AC: 113630 AN: 152018 Hom.: 42654 Cov.: 32 AF XY: 0.749 AC XY: 55661 AN XY: 74302

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.721

Alfa AF: 0.746 Hom.: 8680

Bravo AF: 0.736

Asia WGS AF: 0.806 AC: 2803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;