1-231872801-A-G

Position:

• chr1-231872801-A-G

Variant summary

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

The NM_018662.3(DISC1):​c.1981+54284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,274 control chromosomes in the GnomAD database, including 1,357 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 (1357 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1981+54284A>G		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2647+54284A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+54284A>G		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19199 AN: 152156 Hom.: 1352 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.126 AC: 19228 AN: 152274 Hom.: 1357 Cov.: 33 AF XY: 0.127 AC XY: 9452 AN XY: 74452

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0806 Hom.: 138

Bravo AF: 0.135

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.1
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6668845; hg19: chr1-232008547;