rs7172340

Variant names:

• chr15-68288463-G-A
• rs7172340
• NM_015322.5:c.249-1144G>A

Variant summary

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

The NM_015322.5(FEM1B):​c.249-1144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 152,336 control chromosomes in the GnomAD database, including 71,489 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 0.97 (71489 hom., cov: 32)
• Consequence: FEM1B NM_015322.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015322.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1B	NM_015322.5	MANE Select	c.249-1144G>A		intron	N/A	NP_056137.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1B	ENST00000306917.5	TSL:1 MANE Select	c.249-1144G>A		intron	N/A	ENSP00000307298.4
	FEM1B	ENST00000570067.1	TSL:4	c.-226-1144G>A		intron	N/A	ENSP00000457002.1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147443 AN: 152218 Hom.: 71437 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.971

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

GnomAD4 genome AF: 0.969 AC: 147555 AN: 152336 Hom.: 71489 Cov.: 32 AF XY: 0.969 AC XY: 72176 AN XY: 74496

African (AFR) AF: 0.975 AC: 40515 AN: 41560

American (AMR) AF: 0.961 AC: 14699 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3393 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5183 AN: 5186

South Asian (SAS) AF: 0.971 AC: 4692 AN: 4830

European-Finnish (FIN) AF: 0.958 AC: 10178 AN: 10624

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65644 AN: 68040

Other (OTH) AF: 0.972 AC: 2056 AN: 2116

Alfa AF: 0.967 Hom.: 125314

Bravo AF: 0.970

Asia WGS AF: 0.975 AC: 3393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.21
PhyloP100		-0.22
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: rs7172340; hg19: chr15-68580801;