2-201139953-C-T

Variant names:

• chr2-201139953-C-T
• rs6759004
• NM_003879.7:c.524-404C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003879.7(CFLAR):​c.524-404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 203,356 control chromosomes in the GnomAD database, including 3,421 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 (2925 hom., cov: 32)
  • Exomes 𝑓: 0.12 (496 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 8 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]

IMPDH1P10 (HGNC:33965): (inosine monophosphate dehydrogenase 1 pseudogene 10)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 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.524-404C>T		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.524-404C>T		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.524-404C>T		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.524-404C>T		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.524-404C>T		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.524-404C>T		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27331 AN: 151966 Hom.: 2924 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.121 AC: 6213 AN: 51272 Hom.: 496 Cov.: 0 AF XY: 0.117 AC XY: 3999 AN XY: 34082

African (AFR) AF: 0.279 AC: 125 AN: 448

American (AMR) AF: 0.100 AC: 96 AN: 958

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 153 AN: 996

East Asian (EAS) AF: 0.00456 AC: 3 AN: 658

South Asian (SAS) AF: 0.0514 AC: 690 AN: 13422

European-Finnish (FIN) AF: 0.123 AC: 488 AN: 3974

Middle Eastern (MID) AF: 0.178 AC: 26 AN: 146

European-Non Finnish (NFE) AF: 0.152 AC: 4350 AN: 28650

Other (OTH) AF: 0.140 AC: 282 AN: 2020

GnomAD4 genome AF: 0.180 AC: 27345 AN: 152084 Hom.: 2925 Cov.: 32 AF XY: 0.176 AC XY: 13106 AN XY: 74364

African (AFR) AF: 0.295 AC: 12251 AN: 41464

American (AMR) AF: 0.138 AC: 2111 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.0352 AC: 182 AN: 5176

South Asian (SAS) AF: 0.0454 AC: 219 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1274 AN: 10584

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.150 AC: 10225 AN: 67970

Other (OTH) AF: 0.172 AC: 362 AN: 2106

Alfa AF: 0.171 Hom.: 379

Bravo AF: 0.188

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.4
DANN	Benign	0.90
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6759004; hg19: chr2-202004676;