chr2-201144863-G-A

Variant names:

• chr2-201144863-G-A
• rs10203550
• NM_003879.7:c.607-515G>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.607-515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 150,498 control chromosomes in the GnomAD database, including 3,297 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 0.20 (3297 hom., cov: 32)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.607-515G>A		intron_variant	Intron 5 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.607-515G>A		intron_variant	Intron 5 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29474 AN: 150378 Hom.: 3295 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.196 AC: 29498 AN: 150498 Hom.: 3297 Cov.: 32 AF XY: 0.192 AC XY: 14121 AN XY: 73360

African (AFR) AF: 0.306 AC: 12553 AN: 40978

American (AMR) AF: 0.148 AC: 2241 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 652 AN: 3458

East Asian (EAS) AF: 0.0363 AC: 186 AN: 5126

South Asian (SAS) AF: 0.0589 AC: 280 AN: 4754

European-Finnish (FIN) AF: 0.141 AC: 1437 AN: 10192

Middle Eastern (MID) AF: 0.107 AC: 31 AN: 290

European-Non Finnish (NFE) AF: 0.171 AC: 11572 AN: 67604

Other (OTH) AF: 0.192 AC: 399 AN: 2082

Alfa AF: 0.184 Hom.: 348

Bravo AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.33
PhyloP100		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10203550; hg19: chr2-202009586;