1-159712443-C-T

Position:

• chr1-159712443-C-T

Variant summary

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

The NM_000567.3(CRP):​c.*1082G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,742 control chromosomes in the GnomAD database, including 7,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.31 (7891 hom., cov: 32)
  • Exomes 𝑓: 0.34 (50 hom.)
• Consequence: CRP NM_000567.3 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.313

Genes affected

CRP (HGNC:2367): (C-reactive protein) The protein encoded by this gene belongs to the pentraxin family which also includes serum amyloid P component protein and pentraxin 3. Pentraxins are involved in complement activation and amplification via communication with complement initiation pattern recognition molecules, but also complement regulation via recruitment of complement regulators. The encoded protein has a calcium dependent ligand binding domain with a distinctive flattened beta-jellyroll structure. It exists in two forms as either a pentamer in circulation or as a nonsoluble monomer in tissues. It is involved in several host defense related functions based on its ability to recognize foreign pathogens and damaged cells of the host and to initiate their elimination by interacting with humoral and cellular effector systems in the blood. Consequently, the level of this protein in plasma increases greatly during acute phase response to tissue injury, infection, or other inflammatory stimuli. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRP	NM_000567.3	c.*1082G>A		3_prime_UTR_variant	2/2	ENST00000255030.9	NP_000558.2
CRP	NM_001329057.2	c.*374G>A		3_prime_UTR_variant	3/3		NP_001315986.1
CRP	NM_001329058.2	c.*148G>A		3_prime_UTR_variant	4/4		NP_001315987.1
CRP	NM_001382703.1	c.*1082G>A		3_prime_UTR_variant	3/3		NP_001369632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9	c.*1082G>A		3_prime_UTR_variant	2/2	1	NM_000567.3	ENSP00000255030	P1
CRP	ENST00000437342.1	c.*374G>A		3_prime_UTR_variant	3/3	1		ENSP00000402788
CRP	ENST00000368112.5	c.*374G>A		3_prime_UTR_variant	4/4	2		ENSP00000357093
CRP	ENST00000473196.1	n.617G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47083 AN: 151876 Hom.: 7883 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.345 AC: 257 AN: 746 Hom.: 50 Cov.: 0 AF XY: 0.349 AC XY: 145 AN XY: 416

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.310 AC: 47111 AN: 151996 Hom.: 7891 Cov.: 32 AF XY: 0.314 AC XY: 23355 AN XY: 74292

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.330

Alfa AF: 0.327 Hom.: 9670

Bravo AF: 0.305

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Inflammation Uncertain:1

Uncertain significance, no assertion criteria provided

reference population

iDNA Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs1205; hg19: chr1-159682233;