rs3802780

Variant names:

• chr11-70434886-G-A
• rs3802780
• NM_005231.4:c.1517-140G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005231.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTTN	NM_005231.4	MANE Select	c.1517-140G>A		intron	N/A	NP_005222.2
	CTTN	NM_001184740.2		c.1406-140G>A		intron	N/A	NP_001171669.1
	CTTN	NM_138565.3		c.1406-140G>A		intron	N/A	NP_612632.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTTN	ENST00000301843.13	TSL:1 MANE Select	c.1517-140G>A		intron	N/A	ENSP00000301843.8
	CTTN	ENST00000376561.7	TSL:1	c.1406-140G>A		intron	N/A	ENSP00000365745.3
	CTTN	ENST00000346329.7	TSL:1	c.1406-140G>A		intron	N/A	ENSP00000317189.4

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

African (AFR) AF: 0.267 AC: 5011 AN: 18792

American (AMR) AF: 0.129 AC: 4872 AN: 37784

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 4146 AN: 18692

East Asian (EAS) AF: 0.00779 AC: 279 AN: 35814

South Asian (SAS) AF: 0.286 AC: 18284 AN: 63902

European-Finnish (FIN) AF: 0.265 AC: 9380 AN: 35378

Middle Eastern (MID) AF: 0.221 AC: 641 AN: 2906

European-Non Finnish (NFE) AF: 0.209 AC: 93034 AN: 445610

Other (OTH) AF: 0.213 AC: 7456 AN: 34966

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

African (AFR) AF: 0.268 AC: 11128 AN: 41574

American (AMR) AF: 0.171 AC: 2618 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.00867 AC: 45 AN: 5190

South Asian (SAS) AF: 0.285 AC: 1375 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2825 AN: 10612

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14565 AN: 68016

Other (OTH) AF: 0.238 AC: 504 AN: 2116

Alfa AF: 0.219 Hom.: 4470

Bravo AF: 0.213

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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