rs4980878

Variant names:

• chr12-317911-G-A
• rs4980878
• NM_001042603.3:c.2897+195C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-317911-G-A
• chr12-317911-G-C
• chr12-317911-G-T

Variant summary

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

The NM_001042603.3(KDM5A):​c.2897+195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,002 control chromosomes in the GnomAD database, including 3,743 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 0.21 (3743 hom., cov: 32)
• Consequence: KDM5A NM_001042603.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 3 publications found

Genes affected

KDM5A (HGNC:9886): (lysine demethylase 5A) This gene encodes a member of the Jumonji, AT-rich interactive domain 1 (JARID1) histone demethylase protein family. The encoded protein plays a role in gene regulation through the histone code by specifically demethylating lysine 4 of histone H3. The encoded protein interacts with many other proteins, including retinoblastoma protein, and is implicated in the transcriptional regulation of Hox genes and cytokines. This gene may play a role in tumor progression. [provided by RefSeq, Aug 2013]

KDM5A Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics, G2P
• El Hayek-Chahrour neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM5A	NM_001042603.3	c.2897+195C>T		intron_variant	Intron 19 of 27	ENST00000399788.7	NP_001036068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM5A	ENST00000399788.7	c.2897+195C>T		intron_variant	Intron 19 of 27	1	NM_001042603.3	ENSP00000382688.2
KDM5A	ENST00000544760.1	c.1754+195C>T		intron_variant	Intron 10 of 12	2		ENSP00000440622.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32491 AN: 151884 Hom.: 3738 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.214 AC: 32515 AN: 152002 Hom.: 3743 Cov.: 32 AF XY: 0.218 AC XY: 16166 AN XY: 74292

African (AFR) AF: 0.150 AC: 6232 AN: 41468

American (AMR) AF: 0.162 AC: 2481 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3464

East Asian (EAS) AF: 0.157 AC: 810 AN: 5156

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4814

European-Finnish (FIN) AF: 0.338 AC: 3560 AN: 10544

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16741 AN: 67946

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.155 Hom.: 420

Bravo AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.71
PhyloP100		-1.0
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: rs4980878; hg19: chr12-427077;