rs2970818

Positions:

• chr12-4497002-T-A
• chr12-4497002-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020374.4(C12orf4):​c.1440+3136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,210 control chromosomes in the GnomAD database, including 671 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 0.088 (671 hom., cov: 32)
• Consequence: C12orf4 NM_020374.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C12orf4	NM_020374.4	c.1440+3136A>T		intron_variant		ENST00000261250.8	NP_065107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C12orf4	ENST00000261250.8	c.1440+3136A>T		intron_variant		1	NM_020374.4	ENSP00000261250	P1
C12orf4	ENST00000545746.5	c.1440+3136A>T		intron_variant		1		ENSP00000439996	P1
C12orf4	ENST00000544258.1	c.*352+3136A>T		intron_variant, NMD_transcript_variant		3		ENSP00000444594

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13414 AN: 152092 Hom.: 668 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.0895

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

GnomAD4 genome AF: 0.0882 AC: 13428 AN: 152210 Hom.: 671 Cov.: 32 AF XY: 0.0852 AC XY: 6338 AN XY: 74420

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0941

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.0758 Hom.: 315

Bravo AF: 0.0913

Asia WGS AF: 0.0450 AC: 157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.75

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: rs2970818; hg19: chr12-4606168;