chr2-96601556-T-C

Variant names:

• chr2-96601556-T-C
• rs6749159
• NM_001115016.3:c.2616+87A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115016.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL3	NM_001115016.3	MANE Select	c.2616+87A>G		intron	N/A	NP_001108488.1
	KANSL3	NM_001349256.2		c.2694+87A>G		intron	N/A	NP_001336185.1
	KANSL3	NM_001349257.2		c.2694+87A>G		intron	N/A	NP_001336186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL3	ENST00000431828.6	TSL:1 MANE Select	c.2616+87A>G		intron	N/A	ENSP00000396749.1
	KANSL3	ENST00000354204.10	TSL:1	n.*2458+87A>G		intron	N/A	ENSP00000346144.7
	KANSL3	ENST00000420155.5	TSL:1	n.*128+87A>G		intron	N/A	ENSP00000414426.1

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

GnomAD2 exomes AF: 0.347 AC: 53117 AN: 153230 AF XY: 0.356

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 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

African (AFR) AF: 0.0795 AC: 2442 AN: 30724

American (AMR) AF: 0.541 AC: 16501 AN: 30510

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 6758 AN: 21424

East Asian (EAS) AF: 0.469 AC: 17639 AN: 37578

South Asian (SAS) AF: 0.660 AC: 47735 AN: 72370

European-Finnish (FIN) AF: 0.198 AC: 8738 AN: 44082

Middle Eastern (MID) AF: 0.421 AC: 2282 AN: 5416

European-Non Finnish (NFE) AF: 0.257 AC: 274671 AN: 1067902

Other (OTH) AF: 0.314 AC: 17737 AN: 56508

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

African (AFR) AF: 0.0848 AC: 3522 AN: 41550

American (AMR) AF: 0.400 AC: 6116 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.437 AC: 2260 AN: 5172

South Asian (SAS) AF: 0.660 AC: 3186 AN: 4828

European-Finnish (FIN) AF: 0.193 AC: 2051 AN: 10600

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17818 AN: 67998

Other (OTH) AF: 0.300 AC: 634 AN: 2112

Alfa AF: 0.191 Hom.: 803

Bravo AF: 0.249

Asia WGS AF: 0.545 AC: 1890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
DANN	Benign	0.45
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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