rs11636081

Variant names:

• chr15-68287727-G-A
• rs11636081
• NM_015322.5:c.249-1880G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015322.5(FEM1B):​c.249-1880G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 152,156 control chromosomes in the GnomAD database, including 66 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 0.022 (66 hom., cov: 32)
• Consequence: FEM1B NM_015322.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 2 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=-0.83).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0218 (3313/152156) while in subpopulation AMR AF = 0.0325 (498/15300). AF 95% confidence interval is 0.0302. There are 66 homozygotes in GnomAd4. There are 1651 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3313 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.249-1880G>A		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.249-1880G>A		intron_variant	Intron 1 of 1	1	NM_015322.5	ENSP00000307298.4
FEM1B	ENST00000570067.1	c.-226-1880G>A		intron_variant	Intron 1 of 1	4		ENSP00000457002.1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3314 AN: 152042 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.00578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0218 AC: 3313 AN: 152156 Hom.: 66 Cov.: 32 AF XY: 0.0222 AC XY: 1651 AN XY: 74390

African (AFR) AF: 0.00576 AC: 239 AN: 41498

American (AMR) AF: 0.0325 AC: 498 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4824

European-Finnish (FIN) AF: 0.0392 AC: 414 AN: 10556

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0293 AC: 1992 AN: 68014

Other (OTH) AF: 0.0142 AC: 30 AN: 2108

Alfa AF: 0.0242 Hom.: 7

Bravo AF: 0.0200

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11636081; hg19: chr15-68580065;