1-172448641-A-G

Variant names:

• chr1-172448641-A-G
• rs2157451
• NM_139240.4:c.198+110A>G

Variant summary

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

The ENST00000367727.9(C1orf105):​c.198+110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 643,670 control chromosomes in the GnomAD database, including 246,059 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 0.89 (60102 hom., cov: 31)
  • Exomes 𝑓: 0.87 (185957 hom.)
• Consequence: C1orf105 ENST00000367727.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 4 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_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367727.9. 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.198+110A>G		intron	N/A	NP_640333.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf105	ENST00000367727.9	TSL:1 MANE Select	c.198+110A>G		intron	N/A	ENSP00000356700.4
	C1orf105	ENST00000488100.6	TSL:5	c.111+110A>G		intron	N/A	ENSP00000431442.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134707 AN: 152044 Hom.: 60057 Cov.: 31

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.909

GnomAD4 exome AF: 0.867 AC: 426267 AN: 491508 Hom.: 185957 AF XY: 0.871 AC XY: 228000 AN XY: 261782

African (AFR) AF: 0.967 AC: 13458 AN: 13920

American (AMR) AF: 0.912 AC: 20454 AN: 22418

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 13717 AN: 14662

East Asian (EAS) AF: 1.00 AC: 32819 AN: 32834

South Asian (SAS) AF: 0.936 AC: 45960 AN: 49100

European-Finnish (FIN) AF: 0.778 AC: 30507 AN: 39232

Middle Eastern (MID) AF: 0.960 AC: 2628 AN: 2738

European-Non Finnish (NFE) AF: 0.839 AC: 243020 AN: 289650

Other (OTH) AF: 0.879 AC: 23704 AN: 26954

GnomAD4 genome AF: 0.886 AC: 134811 AN: 152162 Hom.: 60102 Cov.: 31 AF XY: 0.886 AC XY: 65898 AN XY: 74402

African (AFR) AF: 0.965 AC: 40071 AN: 41526

American (AMR) AF: 0.915 AC: 14007 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3261 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5184

South Asian (SAS) AF: 0.944 AC: 4545 AN: 4816

European-Finnish (FIN) AF: 0.766 AC: 8096 AN: 10574

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56675 AN: 67972

Other (OTH) AF: 0.910 AC: 1922 AN: 2112

Alfa AF: 0.872 Hom.: 17050

Bravo AF: 0.901

Asia WGS AF: 0.968 AC: 3367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs2157451; hg19: chr1-172417781;