chr1-172453066-C-A

Position:

• chr1-172453066-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367727.9(C1orf105):​c.199-3349C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,550,492 control chromosomes in the GnomAD database, including 4,222 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 0.095 (2265 hom., cov: 32)
  • Exomes 𝑓: 0.010 (1957 hom.)
• Consequence: C1orf105 ENST00000367727.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

Genes affected

C1orf105 (HGNC:29591): (chromosome 1 open reading frame 105)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.840989).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf105	NM_139240.4	c.199-3349C>A		intron_variant		ENST00000367727.9	NP_640333.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf105	ENST00000367727.9	c.199-3349C>A		intron_variant		1	NM_139240.4	ENSP00000356700	P1
C1orf105	ENST00000367725.4	c.45C>A	p.Cys15Ter	stop_gained	1/5	2		ENSP00000356698
C1orf105	ENST00000488100.6	c.112-3349C>A		intron_variant		5		ENSP00000431442
C1orf105	ENST00000367726.1	n.77+1949C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14458 AN: 152010 Hom.: 2253 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.0738

GnomAD3 exomes AF: 0.0211 AC: 3166 AN: 149890 Hom.: 387 AF XY: 0.0165 AC XY: 1330 AN XY: 80616

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.0219

Gnomad ASJ exome AF: 0.00787

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.00102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00223

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.0105 AC: 14667 AN: 1398364 Hom.: 1957 Cov.: 30 AF XY: 0.00926 AC XY: 6388 AN XY: 689704

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.0233

Gnomad4 ASJ exome AF: 0.00886

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.000947

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.0244

GnomAD4 genome AF: 0.0953 AC: 14497 AN: 152128 Hom.: 2265 Cov.: 32 AF XY: 0.0925 AC XY: 6882 AN XY: 74384

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00188

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0295 Hom.: 384

Bravo AF: 0.109

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00130 AC: 5

ExAC AF: 0.0260 AC: 573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.52
DANN	Benign	0.97
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
MutationTaster	Benign	8.0e-8	P;P
Vest4		0.0090
GERP RS		-2.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7532205; hg19: chr1-172422206; COSMIC: COSV62959545;