chr1-231950407-G-A

Position:

• chr1-231950407-G-A

Variant summary

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

The NM_018662.3(DISC1):​c.1982-8421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,988 control chromosomes in the GnomAD database, including 3,277 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 0.18 (3277 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1982-8421G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2648-8421G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-8421G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26697 AN: 151870 Hom.: 3276 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.176 AC: 26706 AN: 151988 Hom.: 3277 Cov.: 32 AF XY: 0.183 AC XY: 13601 AN XY: 74298

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.205

Alfa AF: 0.157 Hom.: 2800

Bravo AF: 0.182

Asia WGS AF: 0.426 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0060
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12137417; hg19: chr1-232086153;