rs4658954

Positions:

• chr1-231843611-G-A

Variant summary

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

The NM_018662.3(DISC1):​c.1981+25094G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,102 control chromosomes in the GnomAD database, including 32,833 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 0.65 (32833 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998

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]

(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 = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.1981+25094G>A		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.2647+25094G>A		intron_variant, non_coding_transcript_variant
LOC105373170	XR_949268.4	n.185+3908C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+25094G>A		intron_variant		5	NM_018662.3	A2
	ENST00000651424.1	n.148+3908C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99086 AN: 151984 Hom.: 32771 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.652 AC: 99204 AN: 152102 Hom.: 32833 Cov.: 31 AF XY: 0.647 AC XY: 48121 AN XY: 74348

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.626

Alfa AF: 0.621 Hom.: 6046

Bravo AF: 0.660

Asia WGS AF: 0.605 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.27

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: rs4658954; hg19: chr1-231979357;