rs843979

chr1-231994862-C-Gchr1-231994862-C-T

Variant summary

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

The NM_018662.3(DISC1):c.2043-13923C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,010 control chromosomes in the GnomAD database, including 16,084 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 (16084 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2043-13923C>G		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2709-13923C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2043-13923C>G		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65489 AN: 151892 Hom.: 16063 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.431 AC: 65554 AN: 152010 Hom.: 16084 Cov.: 32 AF XY: 0.430 AC XY: 31919 AN XY: 74304

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.382

Alfa AF: 0.205 Hom.: 389

Bravo AF: 0.433

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.8
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs843979; hg19: chr1-232130608; COSMIC: COSV64093716;