rs6494730

Variant names:

• chr15-68292218-G-T
• rs6494730
• NM_015322.5:c.*976G>T

Variant summary

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

The NM_015322.5(FEM1B):​c.*976G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,000 control chromosomes in the GnomAD database, including 9,053 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 (9053 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: FEM1B NM_015322.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.*976G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000306917.5	NP_056137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEM1B	ENST00000306917.5	c.*976G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_015322.5	ENSP00000307298.4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50521 AN: 151882 Hom.: 9048 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.361

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.333 AC: 50545 AN: 152000 Hom.: 9053 Cov.: 33 AF XY: 0.324 AC XY: 24049 AN XY: 74300

African (AFR) AF: 0.419 AC: 17348 AN: 41444

American (AMR) AF: 0.275 AC: 4202 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.0343 AC: 178 AN: 5182

South Asian (SAS) AF: 0.128 AC: 616 AN: 4828

European-Finnish (FIN) AF: 0.278 AC: 2930 AN: 10552

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22894 AN: 67932

Other (OTH) AF: 0.358 AC: 756 AN: 2114

Alfa AF: 0.343 Hom.: 1416

Bravo AF: 0.339

Asia WGS AF: 0.110 AC: 385 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.39
PhyloP100		0.47
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: rs6494730; hg19: chr15-68584556;