chr1-231896069-C-T

Position:

• chr1-231896069-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.1982-62759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,892 control chromosomes in the GnomAD database, including 20,862 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 0.52 (20862 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1982-62759C>T		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2648-62759C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-62759C>T		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79121 AN: 151774 Hom.: 20859 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.521 AC: 79153 AN: 151892 Hom.: 20862 Cov.: 31 AF XY: 0.525 AC XY: 38980 AN XY: 74218

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.521

Alfa AF: 0.529 Hom.: 38175

Bravo AF: 0.504

Asia WGS AF: 0.576 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs967433; hg19: chr1-232031815;