rs3093063

Variant names:

• chr1-159714683-G-A
• rs3093063
• ENST00000751816.1:n.108-11844G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-159714683-G-A
• chr1-159714683-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000751816.1(ENSG00000297913):​n.108-11844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 572,284 control chromosomes in the GnomAD database, including 19 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 0.0074 (12 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (7 hom.)
• Consequence: ENSG00000297913 ENST00000751816.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 7 publications found

Genes affected

ENSG00000297913 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00741 (1128/152242) while in subpopulation AFR AF = 0.025 (1037/41538). AF 95% confidence interval is 0.0237. There are 12 homozygotes in GnomAd4. There are 571 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRP	NM_000567.3	c.-198C>T		upstream_gene_variant		ENST00000255030.9	NP_000558.2
CRP	NM_001329057.2	c.-198C>T		upstream_gene_variant			NP_001315986.1
CRP	NM_001382703.1	c.-198C>T		upstream_gene_variant			NP_001369632.1
CRP	NM_001329058.2	c.-198C>T		upstream_gene_variant			NP_001315987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9	c.-198C>T		upstream_gene_variant		1	NM_000567.3	ENSP00000255030.5

Frequencies

GnomAD3 genomes AF: 0.00736 AC: 1120 AN: 152124 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00122 AC: 511 AN: 420042 Hom.: 7 AF XY: 0.00104 AC XY: 228 AN XY: 218884

African (AFR) AF: 0.0260 AC: 316 AN: 12154

American (AMR) AF: 0.00346 AC: 63 AN: 18220

Ashkenazi Jewish (ASJ) AF: 0.000477 AC: 6 AN: 12590

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.000228 AC: 8 AN: 35080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34228

Middle Eastern (MID) AF: 0.00328 AC: 6 AN: 1832

European-Non Finnish (NFE) AF: 0.000163 AC: 41 AN: 251434

Other (OTH) AF: 0.00292 AC: 71 AN: 24300

GnomAD4 genome AF: 0.00741 AC: 1128 AN: 152242 Hom.: 12 Cov.: 31 AF XY: 0.00767 AC XY: 571 AN XY: 74442

African (AFR) AF: 0.0250 AC: 1037 AN: 41538

American (AMR) AF: 0.00405 AC: 62 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68028

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.00858

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.74
PhyloP100		-0.55
PromoterAI		0.077	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3093063; hg19: chr1-159684473;