Genetic Variant ENSG00000254706:c.-11-3019C>T (chr1-162378872-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000420220.1(ENSG00000254706):c.-11-3019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,300,418 control chromosomes in the GnomAD database, including 649,096 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 1.0 ( 75506 hom., cov: 31)

Exomes 𝑓: 1.0 ( 573590 hom. )

Consequence

ENSG00000254706
ENST00000420220.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Publications

6 publications found

Variant links:

Genes affected

ENSG00000254706 (HGNC:):

ENSG00000254706 links:

C1orf226 (HGNC:34351): (chromosome 1 open reading frame 226)

C1orf226 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf226	NM_001135240.4 link	c.-171C>T		upstream_gene_variant			NP_001128712.2	A1L170-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000254706	ENST00000420220.1 link	c.-11-3019C>T		intron_variant	Intron 2 of 3	5		ENSP00000398035.1		F8W6W0

Frequencies

GnomAD3 genomes

AF:

0.996

AC:

151525

AN:

152162

Hom.:

75448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.985

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD2 exomes

AF:

0.999

AC:

149519

AN:

149656

AF XY:

0.999

show subpopulations

Gnomad AFR exome

AF:

0.984

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1147658

AN:

1148138

Hom.:

573590

Cov.:

AF XY:

1.00

AC XY:

572819

AN XY:

573012

show subpopulations

African (AFR)

AF:

0.986

AC:

26249

AN:

26614

American (AMR)

AF:

0.999

AC:

34810

AN:

34828

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

23164

AN:

23164

East Asian (EAS)

AF:

1.00

AC:

33944

AN:

33944

South Asian (SAS)

AF:

1.00

AC:

73187

AN:

73188

European-Finnish (FIN)

AF:

1.00

AC:

48686

AN:

48686

Middle Eastern (MID)

AF:

1.00

AC:

3633

AN:

3634

European-Non Finnish (NFE)

AF:

1.00

AC:

854714

AN:

854776

Other (OTH)

AF:

0.999

AC:

49271

AN:

49304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15798

31596

47394

63192

78990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.996

AC:

151642

AN:

152280

Hom.:

75506

Cov.:

AF XY:

0.996

AC XY:

74148

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.985

AC:

40940

AN:

41560

American (AMR)

AF:

0.999

AC:

15285

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5154

AN:

5154

South Asian (SAS)

AF:

1.00

AC:

4818

AN:

4818

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68034

AN:

68036

Other (OTH)

AF:

0.999

AC:

2111

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.998

Hom.:

13701

Bravo

AF:

0.995

Asia WGS

AF:

1.00

AC:

3477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0040

(source)

DANN

Benign

0.71

PhyloP100

-1.6

PromoterAI

-0.0026

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over