rs6494730

Positions:

• chr15-68292218-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FEM1B	NM_015322.5	c.*976G>T		3_prime_UTR_variant	2/2	ENST00000306917.5	NP_056137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEM1B	ENST00000306917.5	c.*976G>T		3_prime_UTR_variant	2/2	1	NM_015322.5	ENSP00000307298	P1

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

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

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.0343

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.358

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6494730; hg19: chr15-68584556;