rs872624

chr1-231939154-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.1982-19674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,136 control chromosomes in the GnomAD database, including 4,055 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 0.21 (4055 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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-IT1 (HGNC:41325): (DISC1 intronic transcript 1)

TSNAX-DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1982-19674G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2648-19674G>A		intron_variant, non_coding_transcript_variant
DISC1-IT1	NR_126441.1	n.118-1774G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-19674G>A		intron_variant		5	NM_018662.3	A2
DISC1-IT1	ENST00000456782.1	n.118-1774G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31713 AN: 152018 Hom.: 4050 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.209 AC: 31741 AN: 152136 Hom.: 4055 Cov.: 32 AF XY: 0.213 AC XY: 15835 AN XY: 74400

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.228

Alfa AF: 0.171 Hom.: 1243

Bravo AF: 0.220

Asia WGS AF: 0.418 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.84
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs872624; hg19: chr1-232074900;