chr7-116549129-T-C

Position:

• chr7-116549129-T-C

Variant summary

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

The NM_001753.5(CAV1):​c.196-9817T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,138 control chromosomes in the GnomAD database, including 51,960 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 0.83 (51960 hom., cov: 31)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.37

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.196-9817T>C		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.103-9817T>C		intron_variant
CAV1	NM_001172896.2	c.103-9817T>C		intron_variant
CAV1	NM_001172897.2	c.103-9817T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.196-9817T>C		intron_variant		1	NM_001753.5	P3
	ENST00000452009.1	n.134+2707A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125440 AN: 152020 Hom.: 51919 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.825 AC: 125539 AN: 152138 Hom.: 51960 Cov.: 31 AF XY: 0.827 AC XY: 61520 AN XY: 74384

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.822

Alfa AF: 0.835 Hom.: 24227

Bravo AF: 0.823

Asia WGS AF: 0.885 AC: 3079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.46

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: rs3779514; hg19: chr7-116189183;