rs16836710

Variant names:

• chr2-201135122-C-T
• rs16836710
• NM_003879.7:c.388-850C>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.388-850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,130 control chromosomes in the GnomAD database, including 5,038 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 (5038 hom., cov: 32)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 14 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.388-850C>T		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.388-850C>T		intron	N/A	NP_001120655.1	O15519-1
	CFLAR	NM_001308042.3		c.388-850C>T		intron	N/A	NP_001294971.1	O15519-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.388-850C>T		intron	N/A	ENSP00000312455.2	O15519-1
	CFLAR	ENST00000423241.6	TSL:1	c.388-850C>T		intron	N/A	ENSP00000399420.2	O15519-1
	CFLAR	ENST00000457277.5	TSL:1	c.388-850C>T		intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35970 AN: 152012 Hom.: 5021 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.237 AC: 36031 AN: 152130 Hom.: 5038 Cov.: 32 AF XY: 0.231 AC XY: 17197 AN XY: 74364

African (AFR) AF: 0.384 AC: 15935 AN: 41450

American (AMR) AF: 0.173 AC: 2646 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3472

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5186

South Asian (SAS) AF: 0.116 AC: 562 AN: 4828

European-Finnish (FIN) AF: 0.133 AC: 1402 AN: 10560

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13765 AN: 68020

Other (OTH) AF: 0.229 AC: 484 AN: 2114

Alfa AF: 0.211 Hom.: 14160

Bravo AF: 0.245

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.53
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: rs16836710; hg19: chr2-201999845;