chr5-87315172-A-C

Position:

• chr5-87315172-A-C

Variant summary

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

The NM_002890.3(RASA1):​c.540-16176A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,228 control chromosomes in the GnomAD database, including 3,915 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 (3915 hom., cov: 32)
• Consequence: RASA1 NM_002890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684

Genes affected

RASA1 (HGNC:9871): (RAS p21 protein activator 1) The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Mutations also have been associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM) and Parkes Weber syndrome. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues. [provided by RefSeq, May 2012]

CCNH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASA1	NM_002890.3	c.540-16176A>C		intron_variant		ENST00000274376.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA1	ENST00000274376.11	c.540-16176A>C		intron_variant		1	NM_002890.3	P2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31916 AN: 152110 Hom.: 3918 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.210 AC: 31907 AN: 152228 Hom.: 3915 Cov.: 32 AF XY: 0.213 AC XY: 15814 AN XY: 74404

Gnomad4 AFR AF: 0.0902

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.256

Alfa AF: 0.238 Hom.: 4339

Bravo AF: 0.202

Asia WGS AF: 0.272 AC: 947 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs35148638; hg19: chr5-86610989; COSMIC: COSV57193174; COSMIC: COSV57193174;