NM_015322.5:c.249-1033A>G

Variant names:

• chr15-68288574-A-G
• rs12909277
• NM_015322.5:c.249-1033A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015322.5(FEM1B):​c.249-1033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,046 control chromosomes in the GnomAD database, including 25,109 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 0.56 (25109 hom., cov: 32)
• Consequence: FEM1B NM_015322.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 7 publications found

Genes affected

FEM1B (HGNC:3649): (fem-1 homolog B) This gene encodes an ankyrin repeat protein that belongs to the death receptor-associated family of proteins and plays a role in mediating apoptosis. The encoded protein is also thought to function in the replication stress-induced checkpoint signaling pathway via interaction with checkpoint kinase 1. [provided by RefSeq, Aug 2013]

FEM1B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.249-1033A>G		intron_variant	Intron 1 of 1	ENST00000306917.5	NP_056137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEM1B	ENST00000306917.5	c.249-1033A>G		intron_variant	Intron 1 of 1	1	NM_015322.5	ENSP00000307298.4
FEM1B	ENST00000570067.1	c.-226-1033A>G		intron_variant	Intron 1 of 1	4		ENSP00000457002.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84764 AN: 151928 Hom.: 25087 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.558 AC: 84829 AN: 152046 Hom.: 25109 Cov.: 32 AF XY: 0.570 AC XY: 42338 AN XY: 74322

African (AFR) AF: 0.384 AC: 15906 AN: 41464

American (AMR) AF: 0.641 AC: 9795 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2105 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4999 AN: 5180

South Asian (SAS) AF: 0.824 AC: 3978 AN: 4828

European-Finnish (FIN) AF: 0.645 AC: 6814 AN: 10560

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39332 AN: 67956

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.561 Hom.: 29868

Bravo AF: 0.549

Asia WGS AF: 0.849 AC: 2948 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.75
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12909277; hg19: chr15-68580912;