rs796584585

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_020937.4(FANCM):c.4516-5_4516-2delCTTA variant causes a splice acceptor, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,551,594 control chromosomes in the GnomAD database, including 20,026 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5284 hom., cov: 26)

Exomes 𝑓: 0.13 ( 14742 hom. )

Consequence

FANCM
NM_020937.4 splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

FANCM (HGNC:23168): (FA complementation group M) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

FANCM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.025540914 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.7, offset of 0 (no position change), new splice context is: tgttttctaatttgtcttAGcat. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant 14-45185207-TCTTA-T is Benign according to our data. Variant chr14-45185207-TCTTA-T is described in ClinVar as [Benign]. Clinvar id is 261387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCM	NM_020937.4 link	c.4516-5_4516-2delCTTA		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 17 of 22	ENST00000267430.10	NP_065988.1	Q8IYD8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCM	ENST00000267430.10 link	c.4516-9_4516-6delCTTA		splice_region_variant, intron_variant	Intron 17 of 22	1	NM_020937.4	ENSP00000267430.5		Q8IYD8-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33449

AN:

151814

Hom.:

5247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.161

AC:

39100

AN:

243140

Hom.:

3919

AF XY:

0.156

AC XY:

20512

AN XY:

131516

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.132

AC:

184163

AN:

1399664

Hom.:

14742

AF XY:

0.133

AC XY:

92891

AN XY:

699012

show subpopulations

Gnomad4 AFR exome

AF:

0.451

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.221

AC:

33545

AN:

151930

Hom.:

5284

Cov.:

AF XY:

0.218

AC XY:

16232

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.167

Hom.:

574

Bravo

AF:

0.235

Asia WGS

AF:

0.180

AC:

627

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 05, 2016

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Premature ovarian failure 15

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 33552906) -

Spermatogenic failure 28

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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