rs3802780

Positions:

• chr11-70434886-G-A

Variant summary

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

The NM_005231.4(CTTN):​c.1517-140G>A 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 846,160 control chromosomes in the GnomAD database, including 20,437 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 (4163 hom., cov: 34)
  • Exomes 𝑓: 0.21 (16274 hom.)
• Consequence: CTTN NM_005231.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

Genes affected

CTTN (HGNC:3338): (cortactin) This gene is overexpressed in breast cancer and squamous cell carcinomas of the head and neck. The encoded protein is localized in the cytoplasm and in areas of the cell-substratum contacts. This gene has two roles: (1) regulating the interactions between components of adherens-type junctions and (2) organizing the cytoskeleton and cell adhesion structures of epithelia and carcinoma cells. During apoptosis, the encoded protein is degraded in a caspase-dependent manner. The aberrant regulation of this gene contributes to tumor cell invasion and metastasis. Three splice variants that encode different isoforms have been identified for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTTN	NM_005231.4	c.1517-140G>A		intron_variant		ENST00000301843.13	NP_005222.2
CTTN	NM_001184740.2	c.1406-140G>A		intron_variant			NP_001171669.1
CTTN	NM_138565.3	c.1406-140G>A		intron_variant			NP_612632.1
CTTN	XM_006718447.4	c.1295-140G>A		intron_variant			XP_006718510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTTN	ENST00000301843.13	c.1517-140G>A		intron_variant		1	NM_005231.4	ENSP00000301843	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34195 AN: 152198 Hom.: 4166 Cov.: 34

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.206 AC: 143103 AN: 693844 Hom.: 16274 AF XY: 0.211 AC XY: 77708 AN XY: 368836

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.00779

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.225 AC: 34208 AN: 152316 Hom.: 4163 Cov.: 34 AF XY: 0.227 AC XY: 16887 AN XY: 74484

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00867

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.238

Alfa AF: 0.219 Hom.: 3404

Bravo AF: 0.213

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.61

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: rs3802780; hg19: chr11-70280992; COSMIC: COSV57236043;