rs10190751

Variant names:

• chr2-201141373-G-A
• rs10190751
• NM_003879.7:c.606+934G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127184.4(CFLAR):​c.607-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,555,566 control chromosomes in the GnomAD database, including 34,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5673 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29180 hom.)
• Consequence: CFLAR NM_001127184.4 splice_acceptor, intron
• Scores: Splicing: ADA: 0.00001420
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.935885).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.606+934G>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.606+934G>A		intron_variant	Intron 5 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38170 AN: 151872 Hom.: 5652 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.233

GnomAD3 exomes AF: 0.176 AC: 28696 AN: 163388 Hom.: 3080 AF XY: 0.172 AC XY: 14978 AN XY: 87010

Gnomad AFR exome AF: 0.411

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.0329

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.196 AC: 275573 AN: 1403576 Hom.: 29180 Cov.: 32 AF XY: 0.195 AC XY: 134825 AN XY: 692730

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.0206

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.252 AC: 38241 AN: 151990 Hom.: 5673 Cov.: 32 AF XY: 0.247 AC XY: 18330 AN XY: 74278

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0406

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.239

Alfa AF: 0.217 Hom.: 6973

Bravo AF: 0.257

TwinsUK AF: 0.198 AC: 735

ALSPAC AF: 0.201 AC: 773

ESP6500AA AF: 0.392 AC: 1221

ESP6500EA AF: 0.193 AC: 1377

ExAC AF: 0.116 AC: 12642

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.94	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.8
DANN	Benign	0.24
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00053	N
GERP RS		-4.6

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs10190751; hg19: chr2-202006096; COSMIC: COSV57937077; COSMIC: COSV57937077;