Genetic Variant FOCAD:c.133-47_133-46delGT (chr9-20720318-GGT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001375567.1(FOCAD):c.133-47_133-46delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,368,524 control chromosomes in the GnomAD database, including 710 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 404 hom., cov: 30)

Exomes 𝑓: 0.010 ( 306 hom. )

Consequence

FOCAD
NM_001375567.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.391

Publications

0 publications found

Variant links:

Genes affected

FOCAD (HGNC:23377): (focadhesin) Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

FOCAD Gene-Disease associations (from GenCC):

liver disease, severe congenital
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

FOCAD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 9-20720318-GGT-G is Benign according to our data. Variant chr9-20720318-GGT-G is described in ClinVar as [Benign]. Clinvar id is 1224232.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1 link	c.133-47_133-46delGT		intron_variant	Intron 3 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11 link	c.133-61_133-60delGT		intron_variant	Intron 3 of 43	5	NM_001375567.1	ENSP00000344307.6		Q5VW36
FOCAD	ENST00000380249.5 link	c.133-61_133-60delGT		intron_variant	Intron 5 of 45	1		ENSP00000369599.1		Q5VW36

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6148

AN:

151566

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.00635

Gnomad EAS

AF:

0.00985

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000501

Gnomad OTH

AF:

0.0241

GnomAD4 exome

AF:

0.0103

AC:

12485

AN:

1216844

Hom.:

306

AF XY:

0.00963

AC XY:

5838

AN XY:

606200

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.148

AC:

4285

AN:

28962

American (AMR)

AF:

0.0147

AC:

564

AN:

38470

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

261

AN:

21200

East Asian (EAS)

AF:

0.0205

AC:

719

AN:

35036

South Asian (SAS)

AF:

0.00908

AC:

645

AN:

71058

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

47482

Middle Eastern (MID)

AF:

0.00987

AC:

AN:

5068

European-Non Finnish (NFE)

AF:

0.00546

AC:

5012

AN:

918312

Other (OTH)

AF:

0.0167

AC:

855

AN:

51256

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.380

Heterozygous variant carriers

943

1886

2828

3771

4714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0408

AC:

6189

AN:

151680

Hom.:

404

Cov.:

AF XY:

0.0396

AC XY:

2936

AN XY:

74126

show subpopulations

African (AFR)

AF:

0.138

AC:

5704

AN:

41376

American (AMR)

AF:

0.0203

AC:

309

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00635

AC:

AN:

3464

East Asian (EAS)

AF:

0.00987

AC:

AN:

5166

South Asian (SAS)

AF:

0.00375

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000501

AC:

AN:

67848

Other (OTH)

AF:

0.0238

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

264

529

793

1058

1322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0465

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 05, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.39

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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9-20720318-GGT-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over