Genetic Variant C12orf57:c.-16+70G>A (chr12-6943732-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001301834.1(C12orf57):c.-16+70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000669 in 1,242,512 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

C12orf57
NM_001301834.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0330

Publications

1 publications found

Variant links:

Genes affected

C12orf57 (HGNC:29521): (chromosome 12 open reading frame 57) This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

C12orf57 links:

ENSG00000272173 (HGNC:):

ENSG00000272173 links:

RNU7-1 (HGNC:34033): (RNA, U7 small nuclear 1) Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]

RNU7-1 Gene-Disease associations (from GenCC):

Aicardi-Goutieres syndrome 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia

RNU7-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-6943732-G-A is Benign according to our data. Variant chr12-6943732-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1301045.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0031 (471/152038) while in subpopulation AFR AF = 0.011 (457/41362). AF 95% confidence interval is 0.0102. There are 4 homozygotes in GnomAd4. There are 231 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301834.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf57	NM_001301834.1	c.-16+70G>A	intron	N/A	NP_001288763.1	Q99622
C12orf57	NM_001301836.2	c.13+70G>A	intron	N/A	NP_001288765.1
RNU7-1	NR_023317.1	n.-84G>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C12orf57	ENST00000852280.1		c.-16+70G>A	intron	N/A	ENSP00000522339.1
C12orf57	ENST00000545581.5	TSL:3	c.-16+70G>A	intron	N/A	ENSP00000440602.1	Q99622
ENSG00000272173	ENST00000607421.3	TSL:6	n.992C>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

469

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00288

GnomAD4 exome

AF:

0.000330

AC:

360

AN:

1090474

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

144

AN XY:

532244

show subpopulations

African (AFR)

AF:

0.0146

AC:

327

AN:

22400

American (AMR)

AF:

0.000353

AC:

AN:

17002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13318

East Asian (EAS)

AF:

0.00

AC:

AN:

13534

South Asian (SAS)

AF:

0.00

AC:

AN:

67220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11794

Middle Eastern (MID)

AF:

0.000244

AC:

AN:

4098

European-Non Finnish (NFE)

AF:

0.00000444

AC:

AN:

901104

Other (OTH)

AF:

0.000550

AC:

AN:

40004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00310

AC:

471

AN:

152038

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

231

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0110

AC:

457

AN:

41362

American (AMR)

AF:

0.000523

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00285

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00156

Hom.:

Bravo

AF:

0.00354

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.52

(source)

DANN

Benign

0.59

PhyloP100

0.033

PromoterAI

-0.041

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over