rs3750769

Variant names:

• chr10-70100110-A-C
• rs3750769
• NM_018649.3:c.689-98A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-70100110-A-C
• chr10-70100110-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018649.3(MACROH2A2):​c.689-98A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 486,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MACROH2A2 NM_018649.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 0 publications found

Genes affected

MACROH2A2 (HGNC:14453): (macroH2A.2 histone) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent histone that is a member of the histone H2A family. It replaces conventional H2A histones in a subset of nucleosomes where it represses transcription and may participate in stable X chromosome inactivation. [provided by RefSeq, Oct 2015]

AIFM2 (HGNC:21411): (apoptosis inducing factor mitochondria associated 2) This gene encodes a flavoprotein oxidoreductase that binds single stranded DNA and is thought to contribute to apoptosis in the presence of bacterial and viral DNA. The expression of this gene is also found to be induced by tumor suppressor protein p53 in colon cancer cells. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROH2A2	NM_018649.3	c.689-98A>C		intron_variant	Intron 6 of 8	ENST00000373255.9	NP_061119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROH2A2	ENST00000373255.9	c.689-98A>C		intron_variant	Intron 6 of 8	1	NM_018649.3	ENSP00000362352.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 2 AN: 486170 Hom.: 0 AF XY: 0.00000393 AC XY: 1 AN XY: 254386

African (AFR) AF: 0.0000766 AC: 1 AN: 13054

American (AMR) AF: 0.00 AC: 0 AN: 20368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14758

East Asian (EAS) AF: 0.00 AC: 0 AN: 29800

South Asian (SAS) AF: 0.00 AC: 0 AN: 41314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3650

European-Non Finnish (NFE) AF: 0.00000340 AC: 1 AN: 294176

Other (OTH) AF: 0.00 AC: 0 AN: 26708

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.51
PhyloP100		-1.3

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: rs3750769; hg19: chr10-71859866;