rs11122324

Positions:

• chr1-231723435-G-A
• chr1-231723435-G-C
• chr1-231723435-G-T

Variant summary

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

The ENST00000317586.8(DISC1):​c.*834G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 985,294 control chromosomes in the GnomAD database, including 62,125 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 0.36 (10182 hom., cov: 32)
  • Exomes 𝑓: 0.35 (51943 hom.)
• Consequence: DISC1 ENST00000317586.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1117+21411G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.1838+21411G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1117+21411G>A		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55231 AN: 151922 Hom.: 10168 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.353 AC: 293786 AN: 833252 Hom.: 51943 Cov.: 31 AF XY: 0.352 AC XY: 135580 AN XY: 384796

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.364 AC: 55282 AN: 152042 Hom.: 10182 Cov.: 32 AF XY: 0.357 AC XY: 26554 AN XY: 74316

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.394

Alfa AF: 0.340 Hom.: 10215

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.64
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11122324; hg19: chr1-231859181;