Genetic Variant ENSG00000305204:n.154C>A (chr1-207496010-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000809561.1(ENSG00000305204):n.154C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 506,914 control chromosomes in the GnomAD database, including 1,047 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 0.027 ( 277 hom., cov: 32)

Exomes 𝑓: 0.032 ( 770 hom. )

Consequence

ENSG00000305204
ENST00000809561.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

3 publications found

Variant links:

Genes affected

ENSG00000305204 (HGNC:):

ENSG00000305204 links:

CR1 (HGNC:2334): (complement C3b/C4b receptor 1 (Knops blood group)) This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]

CR1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR1	NM_000651.6 link	c.-258G>T		upstream_gene_variant		ENST00000367049.9	NP_000642.3	P17927E9PDY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR1	ENST00000367049.9 link	c.-258G>T		upstream_gene_variant		5	NM_000651.6	ENSP00000356016.4		E9PDY4

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4127

AN:

152178

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.0998

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00794

Gnomad OTH

AF:

0.0215

GnomAD4 exome

AF:

0.0316

AC:

11190

AN:

354618

Hom.:

770

AF XY:

0.0349

AC XY:

6542

AN XY:

187488

show subpopulations

African (AFR)

AF:

0.0260

AC:

234

AN:

8998

American (AMR)

AF:

0.00561

AC:

AN:

13194

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

332

AN:

10690

East Asian (EAS)

AF:

0.210

AC:

4402

AN:

20928

South Asian (SAS)

AF:

0.0829

AC:

3314

AN:

39992

European-Finnish (FIN)

AF:

0.0158

AC:

317

AN:

20080

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

1566

European-Non Finnish (NFE)

AF:

0.00833

AC:

1822

AN:

218784

Other (OTH)

AF:

0.0333

AC:

678

AN:

20386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

425

850

1275

1700

2125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0270

AC:

4116

AN:

152296

Hom.:

277

Cov.:

AF XY:

0.0301

AC XY:

2242

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0273

AC:

1136

AN:

41568

American (AMR)

AF:

0.0124

AC:

189

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1381

AN:

5162

South Asian (SAS)

AF:

0.0988

AC:

477

AN:

4828

European-Finnish (FIN)

AF:

0.0233

AC:

247

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00794

AC:

540

AN:

68032

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

182

364

546

728

910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0262

Asia WGS

AF:

0.173

AC:

602

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

1.2

(source)

DANN

Benign

0.71

PhyloP100

-1.0

PromoterAI

-0.0032

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over