chr1-42767380-A-C

Position:

• chr1-42767380-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024097.4(C1orf50):​c.69A>C​(p.Ala23Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,538,774 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (30 hom.)
• Consequence: C1orf50 NM_024097.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.932

Genes affected

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-42767380-A-C is Benign according to our data. Variant chr1-42767380-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1196383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.932 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1824/152308) while in subpopulation AFR AF= 0.0412 (1712/41568). AF 95% confidence interval is 0.0396. There are 33 homozygotes in gnomad4. There are 825 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf50	NM_024097.4	c.69A>C	p.Ala23Ala	synonymous_variant	1/5	ENST00000372525.7	NP_077002.2
C1orf50	NR_040733.2	n.132A>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf50	ENST00000372525.7	c.69A>C	p.Ala23Ala	synonymous_variant	1/5	1	NM_024097.4	ENSP00000361603.4
ENSG00000283580	ENST00000603943.6	n.69A>C		non_coding_transcript_exon_variant	1/5	5		ENSP00000473874.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1821 AN: 152190 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00284 AC: 393 AN: 138216 Hom.: 5 AF XY: 0.00225 AC XY: 171 AN XY: 75880

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.000143

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000951

Gnomad FIN exome AF: 0.0000665

Gnomad NFE exome AF: 0.000234

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.00128 AC: 1778 AN: 1386466 Hom.: 30 Cov.: 33 AF XY: 0.00112 AC XY: 769 AN XY: 684710

Gnomad4 AFR exome AF: 0.0459

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.000292

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000901

Gnomad4 FIN exome AF: 0.0000206

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.0120 AC: 1824 AN: 152308 Hom.: 33 Cov.: 33 AF XY: 0.0111 AC XY: 825 AN XY: 74470

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00322 Hom.: 1

Bravo AF: 0.0143

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56073841; hg19: chr1-43233051;