chr12-4517710-CAG-C

Position:

• chr12-4517710-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000261250.8(C12orf4):​c.1033+346_1033+347del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 132,018 control chromosomes in the GnomAD database, including 1,966 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1966 hom., cov: 25)
• Consequence: C12orf4 ENST00000261250.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.199

Genes affected

C12orf4 (HGNC:1184): (FERRY endosomal RAB5 effector complex subunit 3) This gene is highly conserved from nematodes to humans. In rat, the orthologous gene encodes a cytoplasmic protein that is involved in mast cell degranulation. The human gene has been implicated in autosomal recessive intellectual disability. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-4517710-CAG-C is Benign according to our data. Variant chr12-4517710-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1236814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf4	NM_020374.4	c.1033+346_1033+347del		intron_variant		ENST00000261250.8	NP_065107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf4	ENST00000261250.8	c.1033+346_1033+347del		intron_variant		1	NM_020374.4	ENSP00000261250	P1
C12orf4	ENST00000545746.5	c.1033+346_1033+347del		intron_variant		1		ENSP00000439996	P1
C12orf4	ENST00000541014.5	c.514+346_514+347del		intron_variant		5		ENSP00000440820
C12orf4	ENST00000544697.1	c.*173+346_*173+347del		intron_variant, NMD_transcript_variant		5		ENSP00000439471

Frequencies

GnomAD3 genomes AF: 0.162 AC: 21350 AN: 132018 Hom.: 1964 Cov.: 25

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0803

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 21351 AN: 132018 Hom.: 1966 Cov.: 25 AF XY: 0.158 AC XY: 10074 AN XY: 63584

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0803

Gnomad4 EAS AF: 0.0207

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs143057656; hg19: chr12-4626876;