1-231915439-G-T

Position:

• chr1-231915439-G-T

Variant summary

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

The NM_018662.3(DISC1):​c.1982-43389G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,158 control chromosomes in the GnomAD database, including 47,814 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 0.79 (47814 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-43389G>T		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.2648-43389G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-43389G>T		intron_variant		5	NM_018662.3	ENSP00000403888	A2

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120074 AN: 152040 Hom.: 47756 Cov.: 33

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.790 AC: 120192 AN: 152158 Hom.: 47814 Cov.: 33 AF XY: 0.794 AC XY: 59023 AN XY: 74378

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.788

Alfa AF: 0.737 Hom.: 51686

Bravo AF: 0.798

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7541019; hg19: chr1-232051185;