rs16856189

chr1-232017637-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.2307+8588G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,834 control chromosomes in the GnomAD database, including 2,936 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 0.15 (2936 hom., cov: 30)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2307+8588G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2973+8588G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+8588G>A		intron_variant		5	NM_018662.3	A2
DISC1	ENST00000366637.8	c.2241+8654G>A		intron_variant		5		P2
DISC1	ENST00000622252.4	c.*848+8588G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22792 AN: 151716 Hom.: 2926 Cov.: 30

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.150 AC: 22828 AN: 151834 Hom.: 2936 Cov.: 30 AF XY: 0.149 AC XY: 11089 AN XY: 74238

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0734

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0892 Hom.: 612

Bravo AF: 0.166

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.6
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856189; hg19: chr1-232153383;