chr1-172453066-C-A

Variant names:

• chr1-172453066-C-A
• rs7532205
• NM_139240.4:c.199-3349C>A

Variant summary

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

The NM_139240.4(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 NM_139240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139240.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf105	NM_139240.4	MANE Select	c.199-3349C>A		intron	N/A	NP_640333.3
	C1orf105	NM_001300760.1		c.45C>A	p.Cys15*	stop_gained	Exon 1 of 5	NP_001287689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf105	ENST00000367727.9	TSL:1 MANE Select	c.199-3349C>A		intron	N/A	ENSP00000356700.4
	C1orf105	ENST00000367725.4	TSL:2	c.45C>A	p.Cys15*	stop_gained	Exon 1 of 5	ENSP00000356698.4
	C1orf105	ENST00000488100.6	TSL:5	c.112-3349C>A		intron	N/A	ENSP00000431442.1

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

GnomAD2 exomes AF: 0.0211 AC: 3166 AN: 149890 AF XY: 0.0165

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 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

African (AFR) AF: 0.342 AC: 10801 AN: 31598

American (AMR) AF: 0.0233 AC: 832 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00886 AC: 223 AN: 25182

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.000947 AC: 75 AN: 79236

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48214

Middle Eastern (MID) AF: 0.0304 AC: 173 AN: 5696

European-Non Finnish (NFE) AF: 0.00106 AC: 1147 AN: 1078990

Other (OTH) AF: 0.0244 AC: 1413 AN: 58006

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

African (AFR) AF: 0.328 AC: 13599 AN: 41428

American (AMR) AF: 0.0371 AC: 567 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00188 AC: 128 AN: 68026

Other (OTH) AF: 0.0730 AC: 154 AN: 2110

Alfa AF: 0.0607 Hom.: 1353

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 v4.9

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
PhyloP100		-2.0
Vest4		0.0090
GERP RS		-2.2
PromoterAI		-0.068	Neutral
Mutation Taster		=184/16	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: rs7532205; hg19: chr1-172422206; COSMIC: COSV62959545;