chr2-201152685-G-A

Variant names:

• chr2-201152685-G-A
• rs73045343
• NM_003879.7:c.793+2850G>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.793+2850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,142 control chromosomes in the GnomAD database, including 2,979 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 0.18 (2978 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 6 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 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+2850G>A		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.793+2850G>A		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.793+2850G>A		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+2850G>A		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.793+2850G>A		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.793+2850G>A		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27612 AN: 151976 Hom.: 2977 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.146 AC: 7 AN: 48 Hom.: 1 AF XY: 0.184 AC XY: 7 AN XY: 38

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

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: 0.200 AC: 6 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.182 AC: 27626 AN: 152094 Hom.: 2978 Cov.: 32 AF XY: 0.178 AC XY: 13245 AN XY: 74380

African (AFR) AF: 0.296 AC: 12290 AN: 41456

American (AMR) AF: 0.140 AC: 2135 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.0356 AC: 184 AN: 5174

South Asian (SAS) AF: 0.0452 AC: 218 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1281 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10427 AN: 67974

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.172 Hom.: 438

Bravo AF: 0.190

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		1.8
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: rs73045343; hg19: chr2-202017408;