chr2-201142137-A-G

Variant names:

• chr2-201142137-A-G
• rs56160734
• NM_003879.7:c.606+1698A>G

Variant summary

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

The NM_003879.7(CFLAR):​c.606+1698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,880 control chromosomes in the GnomAD database, including 5,158 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 (5158 hom., cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 4 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)

RNU7-45P (HGNC:34141): (RNA, U7 small nuclear 45 pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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.606+1698A>G		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.606+1698A>G		intron	N/A	NP_001120655.1	O15519-1
	CFLAR	NM_001308042.3		c.606+1698A>G		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.606+1698A>G		intron	N/A	ENSP00000312455.2	O15519-1
	CFLAR	ENST00000423241.6	TSL:1	c.606+1698A>G		intron	N/A	ENSP00000399420.2	O15519-1
	CFLAR	ENST00000457277.5	TSL:1	c.606+1698A>G		intron	N/A	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36800 AN: 151762 Hom.: 5139 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.243 AC: 36868 AN: 151880 Hom.: 5158 Cov.: 31 AF XY: 0.238 AC XY: 17676 AN XY: 74228

African (AFR) AF: 0.384 AC: 15893 AN: 41376

American (AMR) AF: 0.174 AC: 2656 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3468

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5180

South Asian (SAS) AF: 0.118 AC: 569 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1695 AN: 10558

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14187 AN: 67916

Other (OTH) AF: 0.232 AC: 488 AN: 2100

Alfa AF: 0.242 Hom.: 600

Bravo AF: 0.248

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.28
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: rs56160734; hg19: chr2-202006860;