NM_003879.7:c.793+3272C>T

Variant names:

• chr2-201153107-C-T
• rs719126
• NM_003879.7:c.793+3272C>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+3272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,298 control chromosomes in the GnomAD database, including 140 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 0.038 (140 hom., cov: 32)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0548 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+3272C>T		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.793+3272C>T		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.793+3272C>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+3272C>T		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.793+3272C>T		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.793+3272C>T		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5833 AN: 152130 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0200 AC: 1 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.0294 AC XY: 1 AN XY: 34

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

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) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0238 AC: 1 AN: 42

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

GnomAD4 genome AF: 0.0385 AC: 5856 AN: 152248 Hom.: 140 Cov.: 32 AF XY: 0.0378 AC XY: 2814 AN XY: 74436

African (AFR) AF: 0.0464 AC: 1927 AN: 41544

American (AMR) AF: 0.0217 AC: 332 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5188

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4824

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0383 AC: 2604 AN: 67992

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0414 Hom.: 15

Bravo AF: 0.0359

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism

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: rs719126; hg19: chr2-202017830;