rs7585993

Variant names:

• chr2-201150391-T-G
• rs7585993
• NM_003879.7:c.793+556T>G

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+556T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 150,620 control chromosomes in the GnomAD database, including 5,621 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 (5614 hom., cov: 30)
  • Exomes 𝑓: 0.19 (7 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 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+556T>G		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.793+556T>G		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.793+556T>G		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+556T>G		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.793+556T>G		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.793+556T>G		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 37897 AN: 150112 Hom.: 5593 Cov.: 30

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.188 AC: 75 AN: 398 Hom.: 7 Cov.: 0 AF XY: 0.164 AC XY: 50 AN XY: 304

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0455 AC: 1 AN: 22

South Asian (SAS) AF: 0.111 AC: 4 AN: 36

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.333 AC: 2 AN: 6

European-Non Finnish (NFE) AF: 0.195 AC: 59 AN: 302

Other (OTH) AF: 0.278 AC: 5 AN: 18

GnomAD4 genome AF: 0.253 AC: 37966 AN: 150222 Hom.: 5614 Cov.: 30 AF XY: 0.248 AC XY: 18174 AN XY: 73256

African (AFR) AF: 0.415 AC: 16954 AN: 40866

American (AMR) AF: 0.178 AC: 2688 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 966 AN: 3456

East Asian (EAS) AF: 0.0409 AC: 206 AN: 5034

South Asian (SAS) AF: 0.120 AC: 568 AN: 4740

European-Finnish (FIN) AF: 0.162 AC: 1657 AN: 10258

Middle Eastern (MID) AF: 0.208 AC: 59 AN: 284

European-Non Finnish (NFE) AF: 0.211 AC: 14212 AN: 67502

Other (OTH) AF: 0.240 AC: 502 AN: 2090

Alfa AF: 0.246 Hom.: 645

Bravo AF: 0.257

Asia WGS AF: 0.125 AC: 438 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	2.3
DANN	Benign	0.42
PhyloP100		-0.51
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: rs7585993; hg19: chr2-202015114;