rs821618

Positions:

• chr1-232009435-G-A
• chr1-232009435-G-T

Variant summary

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

The NM_018662.3(DISC1):​c.2307+386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 575,828 control chromosomes in the GnomAD database, including 23,779 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 0.29 (6287 hom., cov: 31)
  • Exomes 𝑓: 0.28 (17492 hom.)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.2307+386G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2973+386G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+386G>A		intron_variant		5	NM_018662.3	A2
DISC1	ENST00000422590.6	c.*2554G>A		3_prime_UTR_variant, NMD_transcript_variant	11/11	1
DISC1	ENST00000366637.8	c.2241+452G>A		intron_variant		5		P2
DISC1	ENST00000622252.4	c.*848+386G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 42403 AN: 146728 Hom.: 6284 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.238

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.282 AC: 120891 AN: 429066 Hom.: 17492 Cov.: 6 AF XY: 0.283 AC XY: 57107 AN XY: 202126

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.289 AC: 42419 AN: 146762 Hom.: 6287 Cov.: 31 AF XY: 0.289 AC XY: 20619 AN XY: 71466

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.255

Alfa AF: 0.169 Hom.: 327

Bravo AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs821618; hg19: chr1-232145181; COSMIC: COSV64093878; COSMIC: COSV64093878;