1-159714396-T-A

Variant names:

• chr1-159714396-T-A
• rs1417938
• NM_000567.3:c.61+29A>T

Variant summary

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

The NM_000567.3(CRP):​c.61+29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,583,888 control chromosomes in the GnomAD database, including 70,214 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 (5407 hom., cov: 27)
  • Exomes 𝑓: 0.30 (64807 hom.)
• Consequence: CRP NM_000567.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 129 publications found

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]

ENSG00000297913 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRP	NM_000567.3	c.61+29A>T		intron_variant	Intron 1 of 1	ENST00000255030.9	NP_000558.2
CRP	NM_001329057.2	c.61+29A>T		intron_variant	Intron 1 of 2		NP_001315986.1
CRP	NM_001382703.1	c.61+29A>T		intron_variant	Intron 1 of 2		NP_001369632.1
CRP	NM_001329058.2	c.61+29A>T		intron_variant	Intron 1 of 3		NP_001315987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRP	ENST00000255030.9	c.61+29A>T		intron_variant	Intron 1 of 1	1	NM_000567.3	ENSP00000255030.5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 37363 AN: 147286 Hom.: 5405 Cov.: 27

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.259

GnomAD2 exomes AF: 0.279 AC: 69472 AN: 249286 AF XY: 0.278

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.0584

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.298

GnomAD4 exome AF: 0.296 AC: 425804 AN: 1436510 Hom.: 64807 Cov.: 30 AF XY: 0.295 AC XY: 210864 AN XY: 715426

African (AFR) AF: 0.117 AC: 3828 AN: 32612

American (AMR) AF: 0.366 AC: 16092 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7581 AN: 25442

East Asian (EAS) AF: 0.0693 AC: 2643 AN: 38152

South Asian (SAS) AF: 0.234 AC: 20019 AN: 85622

European-Finnish (FIN) AF: 0.358 AC: 18779 AN: 52452

Middle Eastern (MID) AF: 0.219 AC: 1148 AN: 5248

European-Non Finnish (NFE) AF: 0.310 AC: 339446 AN: 1094064

Other (OTH) AF: 0.276 AC: 16268 AN: 58920

GnomAD4 genome AF: 0.254 AC: 37388 AN: 147378 Hom.: 5407 Cov.: 27 AF XY: 0.255 AC XY: 18310 AN XY: 71718

African (AFR) AF: 0.122 AC: 4847 AN: 39802

American (AMR) AF: 0.307 AC: 4534 AN: 14790

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1056 AN: 3448

East Asian (EAS) AF: 0.0649 AC: 307 AN: 4728

South Asian (SAS) AF: 0.252 AC: 1120 AN: 4442

European-Finnish (FIN) AF: 0.356 AC: 3518 AN: 9872

Middle Eastern (MID) AF: 0.226 AC: 65 AN: 288

European-Non Finnish (NFE) AF: 0.314 AC: 21087 AN: 67056

Other (OTH) AF: 0.260 AC: 533 AN: 2050

Alfa AF: 0.278 Hom.: 1231

Bravo AF: 0.244

Asia WGS AF: 0.160 AC: 559 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.77
PhyloP100		-0.60
PromoterAI		-0.0046	Neutral
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: rs1417938; hg19: chr1-159684186; COSMIC: COSV54812545; COSMIC: COSV54812545;