NM_003879.7:c.793+470G>T

Variant names:

• chr2-201150305-G-T
• rs7571899
• NM_003879.7:c.793+470G>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.793+470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 150,912 control chromosomes in the GnomAD database, including 5,025 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 0.24 (5021 hom., cov: 29)
  • Exomes 𝑓: 0.15 (4 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.793+470G>T		intron_variant	Intron 8 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.793+470G>T		intron_variant	Intron 8 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36139 AN: 150332 Hom.: 5002 Cov.: 29

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.149 AC: 69 AN: 464 Hom.: 4 Cov.: 0 AF XY: 0.148 AC XY: 51 AN XY: 344

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 32

South Asian (SAS) AF: 0.143 AC: 6 AN: 42

European-Finnish (FIN) AF: 0.200 AC: 2 AN: 10

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.146 AC: 49 AN: 336

Other (OTH) AF: 0.214 AC: 6 AN: 28

GnomAD4 genome AF: 0.241 AC: 36205 AN: 150448 Hom.: 5021 Cov.: 29 AF XY: 0.236 AC XY: 17291 AN XY: 73418

African (AFR) AF: 0.381 AC: 15472 AN: 40642

American (AMR) AF: 0.174 AC: 2620 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 962 AN: 3460

East Asian (EAS) AF: 0.0395 AC: 203 AN: 5140

South Asian (SAS) AF: 0.117 AC: 560 AN: 4792

European-Finnish (FIN) AF: 0.155 AC: 1598 AN: 10316

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

European-Non Finnish (NFE) AF: 0.208 AC: 14099 AN: 67716

Other (OTH) AF: 0.231 AC: 483 AN: 2088

Alfa AF: 0.131 Hom.: 235

Bravo AF: 0.248

Asia WGS AF: 0.120 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.91
DANN	Benign	0.27
PhyloP100		-0.90
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: rs7571899; hg19: chr2-202015028;