rs12672038

Positions:

• chr7-116547052-G-A

Variant summary

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

The NM_001753.5(CAV1):​c.196-11894G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,160 control chromosomes in the GnomAD database, including 666 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 0.079 (666 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.196-11894G>A		intron_variant		ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.103-11894G>A		intron_variant			NP_001166366.1
CAV1	NM_001172896.2	c.103-11894G>A		intron_variant			NP_001166367.1
CAV1	NM_001172897.2	c.103-11894G>A		intron_variant			NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.196-11894G>A		intron_variant		1	NM_001753.5	ENSP00000339191	P3
	ENST00000452009.1	n.135-4083C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11972 AN: 152042 Hom.: 666 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0787 AC: 11971 AN: 152160 Hom.: 666 Cov.: 32 AF XY: 0.0844 AC XY: 6276 AN XY: 74368

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.0361

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0691 Hom.: 47

Bravo AF: 0.0722

Asia WGS AF: 0.136 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.50

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: rs12672038; hg19: chr7-116187106;