chr4-73581793-A-C

Variant names:

• chr4-73581793-A-C
• rs1247671
• NM_177532.5:c.721+24T>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.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
• Publications: 8 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=-0.83).
• 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 rank	MANE	Protein	UniProt
RASSF6	NM_177532.5	c.721+24T>G		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>G		intron_variant	Intron 8 of 10	1	NM_177532.5	ENSP00000303877.5
RASSF6	ENST00000335049.5	c.685+24T>G		intron_variant	Intron 7 of 9	1		ENSP00000335582.5
RASSF6	ENST00000395777.6	c.619+24T>G		intron_variant	Intron 7 of 9	1		ENSP00000379123.2
RASSF6	ENST00000342081.7	c.817+24T>G		intron_variant	Intron 8 of 10	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

GnomAD2 exomes AF: 0.757 AC: 188920 AN: 249680 AF XY: 0.764

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 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

African (AFR) AF: 0.730 AC: 23540 AN: 32228

American (AMR) AF: 0.611 AC: 27168 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 18381 AN: 25634

East Asian (EAS) AF: 0.880 AC: 34589 AN: 39288

South Asian (SAS) AF: 0.816 AC: 68985 AN: 84498

European-Finnish (FIN) AF: 0.787 AC: 41955 AN: 53298

Middle Eastern (MID) AF: 0.719 AC: 4052 AN: 5632

European-Non Finnish (NFE) AF: 0.756 AC: 797055 AN: 1054342

Other (OTH) AF: 0.751 AC: 43783 AN: 58294

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

African (AFR) AF: 0.739 AC: 30616 AN: 41442

American (AMR) AF: 0.628 AC: 9569 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2479 AN: 3466

East Asian (EAS) AF: 0.886 AC: 4566 AN: 5156

South Asian (SAS) AF: 0.820 AC: 3961 AN: 4830

European-Finnish (FIN) AF: 0.792 AC: 8379 AN: 10578

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.760 AC: 51660 AN: 67992

Other (OTH) AF: 0.721 AC: 1522 AN: 2110

Alfa AF: 0.745 Hom.: 14756

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
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1247671; hg19: chr4-74447510;