chr11-119094338-G-A

Position:

• chr11-119094338-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002105.3(H2AX):​c.*625C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,256 control chromosomes in the GnomAD database, including 7,913 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 (7910 hom., cov: 33)
  • Exomes 𝑓: 0.26 (3 hom.)
• Consequence: H2AX NM_002105.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

H2AX (HGNC:4739): (H2A.X variant histone) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene encodes a replication-independent histone that is a member of the histone H2A family, and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif. [provided by RefSeq, Oct 2015]

DPAGT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H2AX	NM_002105.3	c.*625C>T		3_prime_UTR_variant	1/1	ENST00000530167.2	NP_002096.1
DPAGT1	XM_047426508.1	c.*2539-77C>T		intron_variant			XP_047282464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2AX	ENST00000530167.2	c.*625C>T		3_prime_UTR_variant	1/1		NM_002105.3	ENSP00000434024	P1
H2AX	ENST00000375167.1	c.*504-77C>T		intron_variant, NMD_transcript_variant		2		ENSP00000364310

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46810 AN: 152068 Hom.: 7904 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.257 AC: 18 AN: 70 Hom.: 3 Cov.: 0 AF XY: 0.190 AC XY: 11 AN XY: 58

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.308 AC: 46835 AN: 152186 Hom.: 7910 Cov.: 33 AF XY: 0.309 AC XY: 23020 AN XY: 74420

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.338

Alfa AF: 0.335 Hom.: 3411

Bravo AF: 0.296

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs7350; hg19: chr11-118965048; COSMIC: COSV53829984; COSMIC: COSV53829984;