chr16-57746491-G-A

Variant names:

• chr16-57746491-G-A
• rs12708992
• NM_005886.3:c.289+1980G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005886.3(KATNB1):​c.289+1980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 152,260 control chromosomes in the GnomAD database, including 897 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 0.097 (897 hom., cov: 32)
• Consequence: KATNB1 NM_005886.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 3 publications found

Genes affected

KATNB1 (HGNC:6217): (katanin regulatory subunit B1) Microtubules, polymers of alpha and beta tubulin subunits, form the mitotic spindle of a dividing cell and help to organize membranous organelles during interphase. Katanin is a heterodimer that consists of a 60 kDa ATPase (p60 subunit A 1) and an 80 kDa accessory protein (p80 subunit B 1). The p60 subunit acts to sever and disassemble microtubules, while the p80 subunit targets the enzyme to the centrosome. Katanin is a member of the AAA family of ATPases. [provided by RefSeq, Jul 2008]

KATNB1 Gene-Disease associations (from GenCC):

• lissencephaly 6 with microcephaly

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P
• microlissencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNB1	NM_005886.3	c.289+1980G>A		intron_variant	Intron 4 of 19	ENST00000379661.8	NP_005877.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNB1	ENST00000379661.8	c.289+1980G>A		intron_variant	Intron 4 of 19	5	NM_005886.3	ENSP00000368982.3

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14792 AN: 152142 Hom.: 894 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0523

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.0972 AC: 14807 AN: 152260 Hom.: 897 Cov.: 32 AF XY: 0.0949 AC XY: 7062 AN XY: 74450

African (AFR) AF: 0.160 AC: 6661 AN: 41536

American (AMR) AF: 0.0533 AC: 816 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.0520 AC: 270 AN: 5188

South Asian (SAS) AF: 0.137 AC: 662 AN: 4830

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5515 AN: 68010

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0420 Hom.: 29

Bravo AF: 0.0988

Asia WGS AF: 0.0890 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.87
PhyloP100		-1.6
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: rs12708992; hg19: chr16-57780403;