rs12042938

Positions:

• chr1-231681096-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018662.3(DISC1):​c.68-12730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,058 control chromosomes in the GnomAD database, including 16,661 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 0.46 (16661 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

DISC1 (HGNC:2888): (DISC1 scaffold protein) This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

TSNAX-DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.68-12730C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.789-12730C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.68-12730C>T		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69606 AN: 151940 Hom.: 16623 Cov.: 33

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.458 AC: 69702 AN: 152058 Hom.: 16661 Cov.: 33 AF XY: 0.460 AC XY: 34173 AN XY: 74326

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.451

Alfa AF: 0.410 Hom.: 18979

Bravo AF: 0.471

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.68

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: rs12042938; hg19: chr1-231816842;