rs16856199

Positions:

• chr1-232018366-T-A

Variant summary

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

The NM_018662.3(DISC1):​c.2308-8069T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,238 control chromosomes in the GnomAD database, including 1,853 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 0.098 (1853 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2308-8069T>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2974-8069T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2308-8069T>A		intron_variant		5	NM_018662.3	A2
DISC1	ENST00000366637.8	c.2242-8069T>A		intron_variant		5		P2
DISC1	ENST00000622252.4	c.*849-8069T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14849 AN: 152120 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0977 AC: 14880 AN: 152238 Hom.: 1853 Cov.: 32 AF XY: 0.0948 AC XY: 7055 AN XY: 74448

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0493

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.00960

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0687 Hom.: 145

Bravo AF: 0.108

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856199; hg19: chr1-232154112;