chr2-201153137-G-T

Variant names:

• chr2-201153137-G-T
• rs719125
• NM_003879.7:c.793+3302G>T

Variant summary

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

The NM_003879.7(CFLAR):​c.793+3302G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,140 control chromosomes in the GnomAD database, including 5,406 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 0.25 (5406 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 18 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]

CFLAR-AS1 (HGNC:14437): (CFLAR antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.793+3302G>T		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.793+3302G>T		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.793+3302G>T		intron	N/A	NP_001294971.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.793+3302G>T		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.793+3302G>T		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.793+3302G>T		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37424 AN: 151992 Hom.: 5385 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.0667 AC: 2 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0769 AC: 2 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.246 AC: 37494 AN: 152110 Hom.: 5406 Cov.: 32 AF XY: 0.242 AC XY: 17969 AN XY: 74382

African (AFR) AF: 0.396 AC: 16427 AN: 41462

American (AMR) AF: 0.176 AC: 2689 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3472

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5186

South Asian (SAS) AF: 0.118 AC: 569 AN: 4824

European-Finnish (FIN) AF: 0.161 AC: 1709 AN: 10596

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14216 AN: 67968

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.215 Hom.: 1824

Bravo AF: 0.251

Asia WGS AF: 0.124 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.5
DANN	Benign	0.77
PhyloP100		0.17
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: rs719125; hg19: chr2-202017860;