rs16856202

chr1-232019405-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018662.3(DISC1):c.2308-7030T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 152,294 control chromosomes in the GnomAD database, including 153 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 0.033 (153 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2308-7030T>G		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2974-7030T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2308-7030T>G		intron_variant		5	NM_018662.3	A2
DISC1	ENST00000366637.8	c.2242-7030T>G		intron_variant		5		P2
DISC1	ENST00000622252.4	c.*849-7030T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4964 AN: 152176 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00820

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0326 AC: 4964 AN: 152294 Hom.: 153 Cov.: 32 AF XY: 0.0335 AC XY: 2492 AN XY: 74476

Gnomad4 AFR AF: 0.00818

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0356 Hom.: 307

Bravo AF: 0.0351

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	15
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856202; hg19: chr1-232155151;