1-42767206-A-T

Variant names:

• chr1-42767206-A-T
• rs3738505
• NM_022356.4:c.-235T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022356.4(P3H1):​c.-235T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,346,988 control chromosomes in the GnomAD database, including 39,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4269 hom., cov: 34)
  • Exomes 𝑓: 0.24 (35198 hom.)
• Consequence: P3H1 NM_022356.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.18
• Publications: 7 publications found

Genes affected

P3H1 (HGNC:19316): (prolyl 3-hydroxylase 1) This gene encodes an enzyme that is a member of the collagen prolyl hydroxylase family. These enzymes are localized to the endoplasmic reticulum and their activity is required for proper collagen synthesis and assembly. Mutations in this gene are associated with osteogenesis imperfecta type VIII. Three alternatively spliced transcript variants encoding different isoforms have been described. Other variants may exist, but their biological validity has not been determined. [provided by RefSeq, Aug 2011]

C1orf50 (HGNC:28795): (chromosome 1 open reading frame 50) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000283580 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-42767206-A-T is Benign according to our data. Variant chr1-42767206-A-T is described in CliVar as Benign. Clinvar id is 1235692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H1	NM_022356.4	c.-235T>A		upstream_gene_variant		ENST00000296388.10	NP_071751.3
C1orf50	NM_024097.4	c.-106A>T		upstream_gene_variant		ENST00000372525.7	NP_077002.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H1	ENST00000296388.10	c.-235T>A		upstream_gene_variant		1	NM_022356.4	ENSP00000296388.5
C1orf50	ENST00000372525.7	c.-106A>T		upstream_gene_variant		1	NM_024097.4	ENSP00000361603.4
ENSG00000283580	ENST00000603943.6	n.-106A>T		upstream_gene_variant		5		ENSP00000473874.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34656 AN: 152160 Hom.: 4266 Cov.: 34

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.236 AC: 282303 AN: 1194710 Hom.: 35198 Cov.: 19 AF XY: 0.241 AC XY: 141327 AN XY: 586650

African (AFR) AF: 0.214 AC: 5577 AN: 26056

American (AMR) AF: 0.154 AC: 3095 AN: 20092

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 4546 AN: 18352

East Asian (EAS) AF: 0.355 AC: 12280 AN: 34596

South Asian (SAS) AF: 0.398 AC: 24494 AN: 61610

European-Finnish (FIN) AF: 0.148 AC: 6534 AN: 44154

Middle Eastern (MID) AF: 0.304 AC: 1035 AN: 3406

European-Non Finnish (NFE) AF: 0.227 AC: 212434 AN: 936222

Other (OTH) AF: 0.245 AC: 12308 AN: 50222

GnomAD4 genome AF: 0.228 AC: 34667 AN: 152278 Hom.: 4269 Cov.: 34 AF XY: 0.230 AC XY: 17093 AN XY: 74460

African (AFR) AF: 0.220 AC: 9164 AN: 41566

American (AMR) AF: 0.180 AC: 2748 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2101 AN: 5164

South Asian (SAS) AF: 0.385 AC: 1859 AN: 4834

European-Finnish (FIN) AF: 0.148 AC: 1575 AN: 10616

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15422 AN: 68000

Other (OTH) AF: 0.234 AC: 495 AN: 2114

Alfa AF: 0.208 Hom.: 431

Bravo AF: 0.228

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.72
DANN	Benign	0.45
PhyloP100		-2.2
PromoterAI		0.062	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3738505; hg19: chr1-43232877;