Variant X-136206155-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001159702.3(FHL1):c.-26-252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 441,390 control chromosomes in the GnomAD database, including 299 homozygotes. There are 5,340 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.041 ( 84 hom., 1301 hem., cov: 24)

Exomes 𝑓: 0.038 ( 215 hom. 4039 hem. )

Consequence

FHL1
NM_001159702.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.692

Variant links:

Genes affected

FHL1 (HGNC:3702): (four and a half LIM domains 1) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.[provided by RefSeq, Nov 2009]

FHL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-136206155-C-T is Benign according to our data. Variant chrX-136206155-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187282.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL1	NM_001159699.2 linkuse as main transcript	c.23-252C>T		intron_variant		ENST00000370683.6
FHL1	NM_001159702.3 linkuse as main transcript	c.-26-252C>T		intron_variant		ENST00000394155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL1	ENST00000370683.6 linkuse as main transcript	c.23-252C>T		intron_variant		1	NM_001159699.2	P1	Q13642-5
FHL1	ENST00000394155.8 linkuse as main transcript	c.-26-252C>T		intron_variant		5	NM_001159702.3		Q13642-2

Frequencies

GnomAD3 genomes

AF:

0.0414

AC:

4671

AN:

112833

Hom.:

Cov.:

AF XY:

0.0372

AC XY:

1300

AN XY:

34975

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.0840

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0566

GnomAD4 exome

AF:

0.0377

AC:

12383

AN:

328505

Hom.:

215

Cov.:

AF XY:

0.0360

AC XY:

4039

AN XY:

112259

show subpopulations

Gnomad4 AFR exome

AF:

0.0442

Gnomad4 AMR exome

AF:

0.0329

Gnomad4 ASJ exome

AF:

0.0686

Gnomad4 EAS exome

AF:

0.0000436

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0244

Gnomad4 NFE exome

AF:

0.0451

Gnomad4 OTH exome

AF:

0.0427

GnomAD4 genome

AF:

0.0414

AC:

4669

AN:

112885

Hom.:

Cov.:

AF XY:

0.0371

AC XY:

1301

AN XY:

35037

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00805

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.0454

Gnomad4 OTH

AF:

0.0553

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0435

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

DANN

Benign

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over