rs7546310

Positions:

• chr1-231926074-A-C
• chr1-231926074-A-G

Variant summary

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

The NM_018662.3(DISC1):​c.1982-32754A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,108 control chromosomes in the GnomAD database, including 17,899 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 0.47 (17899 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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]

DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-32754A>C		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-32754A>C		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-32754A>C		intron_variant		5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71164 AN: 151986 Hom.: 17893 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.468 AC: 71178 AN: 152104 Hom.: 17899 Cov.: 33 AF XY: 0.464 AC XY: 34524 AN XY: 74358

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.462

Alfa AF: 0.378 Hom.: 1150

Bravo AF: 0.454

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.78
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7546310; hg19: chr1-232061820;