19-29706248-C-T

Variant names:

• chr19-29706248-C-T
• rs3746314
• NM_031448.6:c.160+2006G>A

Variant summary

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

The NM_031448.6(C19orf12):​c.160+2006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,266 control chromosomes in the GnomAD database, including 1,678 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 0.13 (1678 hom., cov: 33)
• Consequence: C19orf12 NM_031448.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

Genes affected

C19orf12 (HGNC:25443): (chromosome 19 open reading frame 12) This gene encodes a small transmembrane protein. Mutations in this gene are a cause of neurodegeneration with brain iron accumulation-4 (NBIA4), but the specific function of the encoded protein is unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C19orf12	NM_031448.6	c.160+2006G>A		intron_variant	Intron 2 of 2	ENST00000323670.14	NP_113636.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C19orf12	ENST00000323670.14	c.160+2006G>A		intron_variant	Intron 2 of 2	2	NM_031448.6	ENSP00000313332.9

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20479 AN: 152148 Hom.: 1673 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.135 AC: 20506 AN: 152266 Hom.: 1678 Cov.: 33 AF XY: 0.142 AC XY: 10547 AN XY: 74438

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.128

Alfa AF: 0.114 Hom.: 2346

Bravo AF: 0.137

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.31

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: rs3746314; hg19: chr19-30197155;