1-231972068-C-T

Position:

• chr1-231972068-C-T

Variant summary

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

The NM_018662.3(DISC1):​c.2042+13180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,984 control chromosomes in the GnomAD database, including 3,531 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 0.15 (3531 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2042+13180C>T		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.2708+13180C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2042+13180C>T		intron_variant		5	NM_018662.3	ENSP00000403888	A2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23094 AN: 151866 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.152 AC: 23123 AN: 151984 Hom.: 3531 Cov.: 32 AF XY: 0.150 AC XY: 11143 AN XY: 74292

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.0324

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0635 Hom.: 1158

Bravo AF: 0.172

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4658971; hg19: chr1-232107814;