chr14-45194625-G-A

Position:

• chr14-45194625-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020937.4(FANCM):​c.5341-1547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,886 control chromosomes in the GnomAD database, including 7,304 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (7304 hom., cov: 32)
• Consequence: FANCM NM_020937.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCM	NM_020937.4	c.5341-1547G>A		intron_variant		ENST00000267430.10	NP_065988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCM	ENST00000267430.10	c.5341-1547G>A		intron_variant		1	NM_020937.4	ENSP00000267430	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37354 AN: 151768 Hom.: 7266 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.236

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37451 AN: 151886 Hom.: 7304 Cov.: 32 AF XY: 0.244 AC XY: 18079 AN XY: 74244

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.234

Alfa AF: 0.227 Hom.: 1158

Bravo AF: 0.264

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.27

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

Other links and lift over

dbSNP: rs7141145; hg19: chr14-45663828;