rs1393082

Variant names:

• chr5-135371383-C-A
• rs1393082
• NM_138610.3:c.173-1241G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-135371383-C-A
• chr5-135371383-C-T

Variant summary

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

The NM_138610.3(MACROH2A1):​c.173-1241G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,062 control chromosomes in the GnomAD database, including 21,637 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 0.48 (21637 hom., cov: 33)
• Consequence: MACROH2A1 NM_138610.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 4 publications found

Genes affected

MACROH2A1 (HGNC:4740): (macroH2A.1 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 participates in stable X chromosome inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

MACROH2A1 Gene-Disease associations (from GenCC):

• brachydactyly-elbow wrist dysplasia syndrome

  Inheritance: AD 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROH2A1	NM_138610.3	c.173-1241G>T		intron_variant	Intron 2 of 8	ENST00000511689.6	NP_613258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROH2A1	ENST00000511689.6	c.173-1241G>T		intron_variant	Intron 2 of 8	1	NM_138610.3	ENSP00000423563.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72315 AN: 151944 Hom.: 21576 Cov.: 33

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.476 AC: 72436 AN: 152062 Hom.: 21637 Cov.: 33 AF XY: 0.471 AC XY: 35033 AN XY: 74336

African (AFR) AF: 0.851 AC: 35325 AN: 41490

American (AMR) AF: 0.421 AC: 6443 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3472

East Asian (EAS) AF: 0.383 AC: 1982 AN: 5170

South Asian (SAS) AF: 0.467 AC: 2248 AN: 4818

European-Finnish (FIN) AF: 0.210 AC: 2219 AN: 10562

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21380 AN: 67950

Other (OTH) AF: 0.475 AC: 1001 AN: 2108

Alfa AF: 0.361 Hom.: 16932

Bravo AF: 0.509

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.86
DANN	Benign	0.46
PhyloP100		-0.65
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: rs1393082; hg19: chr5-134707073;