18-36885549-T-A

Position:

• chr18-36885549-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020776.3(KIAA1328):​c.333-8T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 1,442,122 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0082 (3 hom.)
• Consequence: KIAA1328 NM_020776.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008961
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.102

Genes affected

KIAA1328 (HGNC:29248): (KIAA1328)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 18-36885549-T-A is Benign according to our data. Variant chr18-36885549-T-A is described in ClinVar as [Benign]. Clinvar id is 770648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1328	NM_020776.3	c.333-8T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000280020.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1328	ENST00000280020.10	c.333-8T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020776.3	P1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151320 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.0000966

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00979 AC: 1254 AN: 128136 Hom.: 0 AF XY: 0.0101 AC XY: 694 AN XY: 68624

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.0179

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00847

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.00949

GnomAD4 exome AF: 0.00821 AC: 10593 AN: 1290688 Hom.: 3 Cov.: 20 AF XY: 0.00810 AC XY: 5182 AN XY: 640104

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00960

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00554

Gnomad4 FIN exome AF: 0.00526

Gnomad4 NFE exome AF: 0.00899

Gnomad4 OTH exome AF: 0.00721

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151434 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 73976

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.0000966

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00397 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000090
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs201927424; hg19: chr18-34465512;