chr1-231877447-T-C

Position:

• chr1-231877447-T-C

Variant summary

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

The NM_018662.3(DISC1):​c.1981+58930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,304 control chromosomes in the GnomAD database, including 61,317 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 0.90 (61317 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+58930T>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.1981+58930T>C		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+58930T>C		intron_variant		5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136454 AN: 152186 Hom.: 61262 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.897 AC: 136568 AN: 152304 Hom.: 61317 Cov.: 33 AF XY: 0.899 AC XY: 66923 AN XY: 74478

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.926

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.900

Alfa AF: 0.888 Hom.: 10602

Bravo AF: 0.899

Asia WGS AF: 0.958 AC: 3329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11122355; hg19: chr1-232013193;