chr2-187554751-G-A

Position:

• chr2-187554751-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000412276.6(CALCRL-AS1):​n.829+358G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,186 control chromosomes in the GnomAD database, including 58,976 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 0.88 (58976 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CALCRL-AS1 ENST00000412276.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

Genes affected

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

TFPI (HGNC:11760): (tissue factor pathway inhibitor) This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCRL-AS1	XR_007087522.1	n.1147+358G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCRL-AS1	ENST00000412276.6	n.829+358G>A		intron_variant, non_coding_transcript_variant		5
TFPI	ENST00000421427.5	c.-274-402C>T		intron_variant		3		ENSP00000408170

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133583 AN: 152066 Hom.: 58930 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.878 AC: 133687 AN: 152186 Hom.: 58976 Cov.: 32 AF XY: 0.874 AC XY: 64978 AN XY: 74386

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.896

Alfa AF: 0.875 Hom.: 7957

Bravo AF: 0.893

Asia WGS AF: 0.823 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10931292; hg19: chr2-188419478;