rs7573256

Variant names:

• chr2-201138447-A-G
• rs7573256
• ENST00000395148.6:c.*2020A>G

Variant summary

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

The NM_001308043.2(CFLAR):​c.*2020A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 850,946 control chromosomes in the GnomAD database, including 19,559 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 0.25 (5738 hom., cov: 32)
  • Exomes 𝑓: 0.18 (13821 hom.)
• Consequence: CFLAR NM_001308043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 10 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308043.2. 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.524-1910A>G		intron	N/A	NP_003870.4
	CFLAR	NM_001308043.2		c.*2020A>G		3_prime_UTR	Exon 5 of 5	NP_001294972.1	E9PAP3
	CFLAR	NM_001127183.4		c.524-1910A>G		intron	N/A	NP_001120655.1	O15519-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000395148.6	TSL:1	c.*2020A>G		3_prime_UTR	Exon 5 of 5	ENSP00000378580.2	E9PAP3
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.524-1910A>G		intron	N/A	ENSP00000312455.2	O15519-1
	CFLAR	ENST00000423241.6	TSL:1	c.524-1910A>G		intron	N/A	ENSP00000399420.2	O15519-1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37734 AN: 151918 Hom.: 5708 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.185 AC: 129139 AN: 698910 Hom.: 13821 Cov.: 9 AF XY: 0.183 AC XY: 68880 AN XY: 376186

African (AFR) AF: 0.429 AC: 8165 AN: 19040

American (AMR) AF: 0.127 AC: 5555 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 5698 AN: 21436

East Asian (EAS) AF: 0.00396 AC: 144 AN: 36356

South Asian (SAS) AF: 0.130 AC: 9233 AN: 71270

European-Finnish (FIN) AF: 0.141 AC: 6351 AN: 44914

Middle Eastern (MID) AF: 0.204 AC: 587 AN: 2884

European-Non Finnish (NFE) AF: 0.203 AC: 86259 AN: 423880

Other (OTH) AF: 0.202 AC: 7147 AN: 35360

GnomAD4 genome AF: 0.249 AC: 37816 AN: 152036 Hom.: 5738 Cov.: 32 AF XY: 0.243 AC XY: 18026 AN XY: 74310

African (AFR) AF: 0.423 AC: 17538 AN: 41438

American (AMR) AF: 0.176 AC: 2693 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 980 AN: 3468

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5178

South Asian (SAS) AF: 0.117 AC: 562 AN: 4824

European-Finnish (FIN) AF: 0.133 AC: 1412 AN: 10600

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13853 AN: 67956

Other (OTH) AF: 0.235 AC: 495 AN: 2102

Alfa AF: 0.243 Hom.: 635

Bravo AF: 0.257

Asia WGS AF: 0.114 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.0
DANN	Benign	0.42
PhyloP100		0.28
Mutation Taster		=99/1	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: rs7573256; hg19: chr2-202003170;