rs10152450

Variant names:

• chr15-68279141-T-G
• rs10152450
• NM_015322.5:c.248+476T>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.248+476T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,022 control chromosomes in the GnomAD database, including 9,091 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 0.33 (9091 hom., cov: 32)
• Consequence: FEM1B NM_015322.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.248+476T>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.248+476T>G		intron_variant	Intron 1 of 1	1	NM_015322.5	ENSP00000307298.4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50640 AN: 151904 Hom.: 9085 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.333 AC: 50666 AN: 152022 Hom.: 9091 Cov.: 32 AF XY: 0.324 AC XY: 24112 AN XY: 74312

African (AFR) AF: 0.419 AC: 17369 AN: 41454

American (AMR) AF: 0.279 AC: 4256 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1253 AN: 3466

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5182

South Asian (SAS) AF: 0.127 AC: 612 AN: 4812

European-Finnish (FIN) AF: 0.276 AC: 2924 AN: 10576

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22946 AN: 67952

Other (OTH) AF: 0.359 AC: 759 AN: 2112

Alfa AF: 0.347 Hom.: 11694

Bravo AF: 0.339

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10152450; hg19: chr15-68571479;