1-231897732-C-T

Position:

• chr1-231897732-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.1982-61096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,178 control chromosomes in the GnomAD database, including 1,241 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 0.12 (1241 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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]

DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-61096C>T		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-61096C>T		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-61096C>T		intron_variant		5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18370 AN: 152060 Hom.: 1236 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.121 AC: 18389 AN: 152178 Hom.: 1241 Cov.: 32 AF XY: 0.122 AC XY: 9063 AN XY: 74402

Gnomad4 AFR AF: 0.0937

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0764

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.131

Alfa AF: 0.119 Hom.: 2314

Bravo AF: 0.130

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6541290; hg19: chr1-232033478;