dbSNP rs3802780: CTTN:c.1517-140G>A (chr11-70434886-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457

Publications

10 publications found

Variant links:

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]

CTTN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CTTN	NM_005231.4 link	c.1517-140G>A	intron_variant	Intron 17 of 17	ENST00000301843.13	NP_005222.2	Q14247-1Q53HG7
CTTN	NM_001184740.2 link	c.1406-140G>A	intron_variant	Intron 16 of 18		NP_001171669.1	Q14247-2
CTTN	NM_138565.3 link	c.1406-140G>A	intron_variant	Intron 16 of 16		NP_612632.1	Q14247-3A0A024R5M3Q53HG7
CTTN	XM_006718447.4 link	c.1295-140G>A	intron_variant	Intron 15 of 15		XP_006718510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTTN	ENST00000301843.13 link	c.1517-140G>A		intron_variant	Intron 17 of 17	1	NM_005231.4	ENSP00000301843.8		Q14247-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34195

AN:

152198

Hom.:

4166

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5408

10816

16223

21631

27039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1590

3180

4770

6360

7950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.225

AC:

34208

AN:

152316

Hom.:

4163

Cov.:

AF XY:

0.227

AC XY:

16887

AN XY:

74484

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14565

AN:

68016

Other (OTH)

AF:

0.238

AC:

504

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1378

2756

4135

5513

6891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

(source)

DANN

Benign

0.61

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over