rs3807989

Positions:

• chr7-116546187-A-G

Variant summary

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

The NM_001753.5(CAV1):​c.196-12759A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,004 control chromosomes in the GnomAD database, including 22,710 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 0.53 (22710 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

CAV1 (HGNC:1527): (caveolin 1) The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. Caveolin 1 and caveolin 2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. Mutations in this gene have been associated with Berardinelli-Seip congenital lipodystrophy. Alternatively spliced transcripts encode alpha and beta isoforms of caveolin 1.[provided by RefSeq, Mar 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.196-12759A>G		intron_variant		ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.103-12759A>G		intron_variant			NP_001166366.1
CAV1	NM_001172896.2	c.103-12759A>G		intron_variant			NP_001166367.1
CAV1	NM_001172897.2	c.103-12759A>G		intron_variant			NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.196-12759A>G		intron_variant		1	NM_001753.5	ENSP00000339191	P3
	ENST00000452009.1	n.135-3218T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80903 AN: 151886 Hom.: 22702 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.532 AC: 80937 AN: 152004 Hom.: 22710 Cov.: 32 AF XY: 0.536 AC XY: 39780 AN XY: 74282

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.549

Alfa AF: 0.592 Hom.: 61758

Bravo AF: 0.526

Asia WGS AF: 0.663 AC: 2301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.81

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: rs3807989; hg19: chr7-116186241;