chr1-23028384-T-A

Variant names:

• chr1-23028384-T-A
• rs7548692
• NM_001009999.3:c.352-2085T>A

Variant summary

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

The NM_001009999.3(KDM1A):​c.352-2085T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,142 control chromosomes in the GnomAD database, including 7,303 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 0.31 (7303 hom., cov: 32)
• Consequence: KDM1A NM_001009999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 6 publications found

Genes affected

KDM1A (HGNC:29079): (lysine demethylase 1A) This gene encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amine oxidase domain. This protein is a component of several histone deacetylase complexes, though it silences genes by functioning as a histone demethylase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KDM1A Gene-Disease associations (from GenCC):

• palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000240553 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1A	NM_001009999.3	MANE Select	c.352-2085T>A		intron	N/A	NP_001009999.1	O60341-2
	KDM1A	NM_001410762.1		c.352-2085T>A		intron	N/A	NP_001397691.1	A0A8I5KXU4
	KDM1A	NM_001363654.2		c.352-2085T>A		intron	N/A	NP_001350583.1	R4GMQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM1A	ENST00000400181.9	TSL:1 MANE Select	c.352-2085T>A		intron	N/A	ENSP00000383042.5	O60341-2
	KDM1A	ENST00000356634.7	TSL:1	c.352-2085T>A		intron	N/A	ENSP00000349049.3	O60341-1
	KDM1A	ENST00000874661.1		c.352-2085T>A		intron	N/A	ENSP00000544720.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46898 AN: 152024 Hom.: 7293 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.309 AC: 46941 AN: 152142 Hom.: 7303 Cov.: 32 AF XY: 0.308 AC XY: 22943 AN XY: 74370

African (AFR) AF: 0.284 AC: 11791 AN: 41502

American (AMR) AF: 0.282 AC: 4311 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1262 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1344 AN: 5166

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3659 AN: 10578

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22197 AN: 68002

Other (OTH) AF: 0.327 AC: 689 AN: 2110

Alfa AF: 0.306 Hom.: 890

Bravo AF: 0.305

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		0.22
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: rs7548692; hg19: chr1-23354877; COSMIC: COSV63087046;