chr2-201171755-G-A

Variant names:

• chr2-201171755-G-A
• rs7558475
• NM_003879.7:c.*7782G>A

Variant summary

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

The NM_003879.7(CFLAR):​c.*7782G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,096 control chromosomes in the GnomAD database, including 61,651 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 0.90 (61651 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: CFLAR NM_003879.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 14 publications found

Genes affected

CFLAR (HGNC:1876): (CASP8 and FADD like apoptosis regulator) The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003879.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.*7782G>A		3_prime_UTR	Exon 10 of 10	NP_003870.4
	CFLAR	NM_001127183.4		c.*7782G>A		3_prime_UTR	Exon 10 of 10	NP_001120655.1
	CFLAR	NM_001308042.3		c.*8675G>A		3_prime_UTR	Exon 10 of 10	NP_001294971.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.*7782G>A		3_prime_UTR	Exon 10 of 10	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136569 AN: 151980 Hom.: 61607 Cov.: 30

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.902

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: 0.899 AC: 136671 AN: 152096 Hom.: 61651 Cov.: 30 AF XY: 0.895 AC XY: 66557 AN XY: 74332

African (AFR) AF: 0.854 AC: 35369 AN: 41416

American (AMR) AF: 0.892 AC: 13640 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3328 AN: 3470

East Asian (EAS) AF: 0.854 AC: 4431 AN: 5186

South Asian (SAS) AF: 0.710 AC: 3419 AN: 4818

European-Finnish (FIN) AF: 0.973 AC: 10296 AN: 10584

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.930 AC: 63277 AN: 68014

Other (OTH) AF: 0.903 AC: 1905 AN: 2110

Alfa AF: 0.918 Hom.: 116269

Bravo AF: 0.891

Asia WGS AF: 0.763 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		0.10
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: rs7558475; hg19: chr2-202036478;