rs6749159

chr2-96601556-T-Cchr2-96601556-T-G

Variant summary

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

The NM_001115016.3(KANSL3):c.2616+87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,518,732 control chromosomes in the GnomAD database, including 72,117 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 0.24 (6002 hom., cov: 32)
  • Exomes 𝑓: 0.29 (66115 hom.)
• Consequence: KANSL3 NM_001115016.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

Genes affected

KANSL3 (HGNC:25473): (KAT8 regulatory NSL complex subunit 3) Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL3	NM_001115016.3	c.2616+87A>G		intron_variant		ENST00000431828.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL3	ENST00000431828.6	c.2616+87A>G		intron_variant		1	NM_001115016.3	P3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36934 AN: 152100 Hom.: 5985 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.294

GnomAD3 exomes AF: 0.347 AC: 53117 AN: 153230 Hom.: 11698 AF XY: 0.356 AC XY: 29246 AN XY: 82208

Gnomad AFR exome AF: 0.0784

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.427

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.289 AC: 394503 AN: 1366514 Hom.: 66115 Cov.: 32 AF XY: 0.300 AC XY: 201278 AN XY: 671650

Gnomad4 AFR exome AF: 0.0795

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.660

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.243 AC: 36967 AN: 152218 Hom.: 6002 Cov.: 32 AF XY: 0.249 AC XY: 18516 AN XY: 74420

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.300

Alfa AF: 0.193 Hom.: 798

Bravo AF: 0.249

Asia WGS AF: 0.545 AC: 1890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.0050
Dann	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6749159; hg19: chr2-97267293; COSMIC: COSV62617534; COSMIC: COSV62617534;