Genetic Variant NM_001375567.1:c.-32-44G>T (chr9-20715278-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001375567.1(FOCAD):c.-32-44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 896,400 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 173 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 68 hom. )

Consequence

FOCAD
NM_001375567.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.15

Publications

1 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-20715278-G-T is Benign according to our data. Variant chr9-20715278-G-T is described in ClinVar as [Benign]. Clinvar id is 1269550.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1 link	c.-32-44G>T		intron_variant	Intron 1 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.-32-44G>T		intron_variant	Intron 1 of 43	5	NM_001375567.1	ENSP00000344307.6		Q5VW36
FOCAD	ENST00000380249.5 link	c.-32-44G>T		intron_variant	Intron 3 of 45	1		ENSP00000369599.1		Q5VW36

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3730

AN:

152142

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0836

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00291

AC:

2167

AN:

744140

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

930

AN XY:

378138

show subpopulations

African (AFR)

AF:

0.0881

AC:

1504

AN:

17074

American (AMR)

AF:

0.00639

AC:

156

AN:

24406

Ashkenazi Jewish (ASJ)

AF:

0.00248

AC:

AN:

16906

East Asian (EAS)

AF:

0.0000339

AC:

AN:

29490

South Asian (SAS)

AF:

0.000281

AC:

AN:

32076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39766

Middle Eastern (MID)

AF:

0.00661

AC:

AN:

3932

European-Non Finnish (NFE)

AF:

0.000347

AC:

190

AN:

547374

Other (OTH)

AF:

0.00722

AC:

239

AN:

33116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

179

269

358

448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0246

AC:

3739

AN:

152260

Hom.:

173

Cov.:

AF XY:

0.0232

AC XY:

1728

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0835

AC:

3470

AN:

41540

American (AMR)

AF:

0.0114

AC:

174

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

68016

Other (OTH)

AF:

0.0194

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

170

340

511

681

851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0279

Asia WGS

AF:

0.00433

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 26, 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

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.16

(source)

DANN

Benign

0.45

PhyloP100

-1.1

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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NM_001375567.1:c.-32-44G>T

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