rs1772702

Positions:

• chr1-232002653-T-G

Variant summary

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

The NM_018662.3(DISC1):​c.2043-6132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 150,528 control chromosomes in the GnomAD database, including 17,030 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 0.43 (17030 hom., cov: 30)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2043-6132T>G		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2709-6132T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2043-6132T>G		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 64611 AN: 150410 Hom.: 16991 Cov.: 30

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.430 AC: 64701 AN: 150528 Hom.: 17030 Cov.: 30 AF XY: 0.427 AC XY: 31353 AN XY: 73408

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.370

Alfa AF: 0.376 Hom.: 1562

Bravo AF: 0.430

Asia WGS AF: 0.364 AC: 1267 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
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: rs1772702; hg19: chr1-232138399;