Genetic Variant FOCAD:c.494+116T>A (chr9-20758307-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001375567.1(FOCAD):c.494+116T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 590,904 control chromosomes in the GnomAD database, including 18,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3862 hom., cov: 31)

Exomes 𝑓: 0.25 ( 14197 hom. )

Consequence

FOCAD
NM_001375567.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.363

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-20758307-T-A is Benign according to our data. Variant chr9-20758307-T-A is described in ClinVar as Benign. ClinVar VariationId is 1288052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375567.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FOCAD	NM_001375567.1	MANE Select	c.494+116T>A	intron	N/A	NP_001362496.1	Q5VW36
FOCAD	NM_017794.5		c.494+116T>A	intron	N/A	NP_060264.4
FOCAD	NM_001375568.1		c.494+116T>A	intron	N/A	NP_001362497.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FOCAD	ENST00000338382.11	TSL:5 MANE Select	c.494+116T>A	intron	N/A	ENSP00000344307.6	Q5VW36
FOCAD	ENST00000380249.5	TSL:1	c.494+116T>A	intron	N/A	ENSP00000369599.1	Q5VW36
FOCAD	ENST00000894775.1		c.494+116T>A	intron	N/A	ENSP00000564834.1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32697

AN:

151910

Hom.:

3859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0483

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.246

AC:

107893

AN:

438876

Hom.:

14197

AF XY:

0.251

AC XY:

57774

AN XY:

230452

show subpopulations

African (AFR)

AF:

0.139

AC:

1504

AN:

10840

American (AMR)

AF:

0.209

AC:

2424

AN:

11600

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

2085

AN:

11882

East Asian (EAS)

AF:

0.0760

AC:

1992

AN:

26218

South Asian (SAS)

AF:

0.318

AC:

9877

AN:

31096

European-Finnish (FIN)

AF:

0.252

AC:

7945

AN:

31588

Middle Eastern (MID)

AF:

0.288

AC:

823

AN:

2856

European-Non Finnish (NFE)

AF:

0.262

AC:

75792

AN:

289494

Other (OTH)

AF:

0.234

AC:

5451

AN:

23302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3739

7478

11218

14957

18696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1124

2248

3372

4496

5620

<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:

0.215

AC:

32712

AN:

152028

Hom.:

3862

Cov.:

AF XY:

0.214

AC XY:

15924

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.143

AC:

5957

AN:

41522

American (AMR)

AF:

0.216

AC:

3290

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

633

AN:

3464

East Asian (EAS)

AF:

0.0484

AC:

251

AN:

5184

South Asian (SAS)

AF:

0.323

AC:

1552

AN:

4810

European-Finnish (FIN)

AF:

0.255

AC:

2678

AN:

10516

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17500

AN:

67954

Other (OTH)

AF:

0.230

AC:

486

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1252

2503

3755

5006

6258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.230

Hom.:

602

Bravo

AF:

0.208

Asia WGS

AF:

0.182

AC:

631

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

(source)

DANN

Benign

0.56

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over