rs61917871

Variant names:

• chr12-6943815-G-A
• rs61917871
• NM_001301834.1:c.-16+153G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6943815-G-A
• chr12-6943815-G-C
• chr12-6943815-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001301834.1(C12orf57):​c.-16+153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 842,698 control chromosomes in the GnomAD database, including 942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (101 hom., cov: 33)
  • Exomes 𝑓: 0.044 (841 hom.)
• Consequence: C12orf57 NM_001301834.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.77
• Publications: 2 publications found

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]

ENSG00000272173 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-6943815-G-A is Benign according to our data. Variant chr12-6943815-G-A is described in ClinVar as Benign. ClinVar VariationId is 1247634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	NM_001301834.1		c.-16+153G>A		intron	N/A	NP_001288763.1	Q99622
	C12orf57	NM_001301836.2		c.13+153G>A		intron	N/A	NP_001288765.1
	C12orf57	NM_138425.4	MANE Select	c.-307G>A		upstream_gene	N/A	NP_612434.1	Q99622

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C12orf57	ENST00000852280.1		c.-16+153G>A		intron	N/A	ENSP00000522339.1
	C12orf57	ENST00000545581.5	TSL:3	c.-16+153G>A		intron	N/A	ENSP00000440602.1	Q99622
	ENSG00000272173	ENST00000607421.3	TSL:6	n.909C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5118 AN: 152204 Hom.: 102 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0383

GnomAD4 exome AF: 0.0443 AC: 30585 AN: 690376 Hom.: 841 Cov.: 9 AF XY: 0.0427 AC XY: 14801 AN XY: 346968

African (AFR) AF: 0.00744 AC: 116 AN: 15582

American (AMR) AF: 0.0305 AC: 448 AN: 14710

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 697 AN: 11692

East Asian (EAS) AF: 0.000693 AC: 14 AN: 20214

South Asian (SAS) AF: 0.0108 AC: 553 AN: 51000

European-Finnish (FIN) AF: 0.0291 AC: 441 AN: 15132

Middle Eastern (MID) AF: 0.0320 AC: 71 AN: 2220

European-Non Finnish (NFE) AF: 0.0511 AC: 27067 AN: 529958

Other (OTH) AF: 0.0394 AC: 1178 AN: 29868

GnomAD4 genome AF: 0.0336 AC: 5115 AN: 152322 Hom.: 101 Cov.: 33 AF XY: 0.0328 AC XY: 2443 AN XY: 74494

African (AFR) AF: 0.0102 AC: 426 AN: 41562

American (AMR) AF: 0.0340 AC: 520 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 255 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4834

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0501 AC: 3409 AN: 68030

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0286 Hom.: 24

Bravo AF: 0.0332

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0010
DANN	Benign	0.65
PhyloP100		-5.8
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61917871; hg19: chr12-7052978;