rs10256914

Positions:

• chr7-116535657-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001753.5(CAV1):​c.195+8968T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,152 control chromosomes in the GnomAD database, including 3,901 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 0.22 (3901 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.195+8968T>C		intron_variant		ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.102+8968T>C		intron_variant			NP_001166366.1
CAV1	NM_001172896.2	c.102+8968T>C		intron_variant			NP_001166367.1
CAV1	NM_001172897.2	c.102+8968T>C		intron_variant			NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.195+8968T>C		intron_variant		1	NM_001753.5	ENSP00000339191	P3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32963 AN: 152034 Hom.: 3904 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.217 AC: 32961 AN: 152152 Hom.: 3901 Cov.: 32 AF XY: 0.209 AC XY: 15516 AN XY: 74386

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.238

Alfa AF: 0.257 Hom.: 10421

Bravo AF: 0.222

Asia WGS AF: 0.0950 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
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: rs10256914; hg19: chr7-116175711;