rs9431714

chr1-231885502-G-Achr1-231885502-G-C

Variant summary

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

The NM_018662.3(DISC1):c.1981+66985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,056 control chromosomes in the GnomAD database, including 8,924 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 0.34 (8924 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

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 (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1981+66985G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2647+66985G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+66985G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51513 AN: 151936 Hom.: 8927 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.339 AC: 51527 AN: 152056 Hom.: 8924 Cov.: 32 AF XY: 0.340 AC XY: 25229 AN XY: 74310

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.341

Alfa AF: 0.362 Hom.: 20535

Bravo AF: 0.333

Asia WGS AF: 0.255 AC: 888 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	6.9
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9431714; hg19: chr1-232021248;