2-201123515-G-A

Variant names:

• chr2-201123515-G-A
• rs7583529
• NM_003879.7:c.-137-6214G>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.-137-6214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,850 control chromosomes in the GnomAD database, including 7,770 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 0.28 (7770 hom., cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 20 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]

ENSG00000299419 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 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.-137-6214G>A		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.-138+4614G>A		intron	N/A	NP_001120655.1
	CFLAR	NM_001351590.2		c.-137-6214G>A		intron	N/A	NP_001338519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.-137-6214G>A		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.-138+4614G>A		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000341582.10	TSL:1	c.-137-6214G>A		intron	N/A	ENSP00000345807.6

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42168 AN: 151732 Hom.: 7757 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.249

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42231 AN: 151850 Hom.: 7770 Cov.: 31 AF XY: 0.271 AC XY: 20121 AN XY: 74224

African (AFR) AF: 0.520 AC: 21515 AN: 41338

American (AMR) AF: 0.188 AC: 2869 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3466

East Asian (EAS) AF: 0.0124 AC: 64 AN: 5180

South Asian (SAS) AF: 0.116 AC: 559 AN: 4812

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10568

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14112 AN: 67914

Other (OTH) AF: 0.255 AC: 537 AN: 2108

Alfa AF: 0.221 Hom.: 8162

Bravo AF: 0.292

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.31
PhyloP100		-0.37
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: rs7583529; hg19: chr2-201988238;