17-46215654-G-T

Variant names:

• chr17-46215654-G-T
• rs2668692
• NM_001379198.1:c.-90+8017C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001379198.1(KANSL1):​c.-90+8017C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 (0 hom., cov: 35)
• Consequence: KANSL1 NM_001379198.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

Genes affected

KANSL1 (HGNC:24565): (KAT8 regulatory NSL complex subunit 1) This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The encoded protein has been implicated in a variety of cellular processes including enhancer regulation, cell proliferation, and mitosis. Mutations in this gene are associated with Koolen-de Vries Syndrome. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000164 (25/152102) while in subpopulation NFE AF= 0.000338 (23/67998). AF 95% confidence interval is 0.00023. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_001379198.1	c.-90+8017C>A		intron_variant	Intron 2 of 15		NP_001366127.1
KANSL1	NM_001405854.1	c.-90+8017C>A		intron_variant	Intron 2 of 15		NP_001392783.1
KANSL1	NM_001193465.2	c.-90+8017C>A		intron_variant	Intron 2 of 15		NP_001180394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000572904.6	c.-90+8017C>A		intron_variant	Intron 1 of 14	5		ENSP00000461484.1
KANSL1	ENST00000574590.6	c.-90+8017C>A		intron_variant	Intron 2 of 15	2		ENSP00000461812.2
KANSL1	ENST00000648792.1	c.-90+8017C>A		intron_variant	Intron 2 of 15			ENSP00000497628.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152102 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152102 Hom.: 0 Cov.: 35 AF XY: 0.000121 AC XY: 9 AN XY: 74300

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.6
DANN	Benign	0.85

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: rs2668692; hg19: chr17-44293020;