rs671357

Variant names:

• chr1-23036551-G-A
• rs671357
• NM_001009999.3:c.517+5917G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-23036551-G-A
• chr1-23036551-G-C

Variant summary

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

The NM_001009999.3(KDM1A):​c.517+5917G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 150,230 control chromosomes in the GnomAD database, including 49,810 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 0.81 (49810 hom., cov: 23)
• Consequence: KDM1A NM_001009999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• Publications: 2 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000240553 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1A	NM_001009999.3	c.517+5917G>A		intron_variant	Intron 2 of 20	ENST00000400181.9	NP_001009999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM1A	ENST00000400181.9	c.517+5917G>A		intron_variant	Intron 2 of 20	1	NM_001009999.3	ENSP00000383042.5

Frequencies

GnomAD3 genomes AF: 0.811 AC: 121781 AN: 150112 Hom.: 49774 Cov.: 23

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.811 AC: 121871 AN: 150230 Hom.: 49810 Cov.: 23 AF XY: 0.807 AC XY: 59085 AN XY: 73206

African (AFR) AF: 0.833 AC: 34002 AN: 40800

American (AMR) AF: 0.668 AC: 9996 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2794 AN: 3468

East Asian (EAS) AF: 0.803 AC: 4010 AN: 4992

South Asian (SAS) AF: 0.590 AC: 2774 AN: 4702

European-Finnish (FIN) AF: 0.885 AC: 9058 AN: 10236

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.835 AC: 56600 AN: 67802

Other (OTH) AF: 0.792 AC: 1642 AN: 2072

Alfa AF: 0.826 Hom.: 10184

Bravo AF: 0.797

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.56
PhyloP100		0.81
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: rs671357; hg19: chr1-23363044;