1-149845941-T-C

Position:

• chr1-149845941-T-C

Variant summary

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

The XM_024451708.2(H4C15):​c.*9145A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,260 control chromosomes in the GnomAD database, including 252 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 0.050 (252 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: H4C15 XM_024451708.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

Genes affected

H4C15 (HGNC:29607): (H4 clustered histone 15) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an 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-dependent histone that is a member of the histone H4 family. Some transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in a histone cluster on chromosome 1. This gene is one of four histone genes in the cluster that are duplicated; this record represents the telomeric copy. [provided by RefSeq, May 2020]

ENSG00000290792 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H4C15	XM_024451708.2	c.*9145A>G		3_prime_UTR_variant	2/2		XP_024307476.2
H4C15	XM_047424434.1	c.*9715A>G		3_prime_UTR_variant	3/3		XP_047280390.1
H4C15	XM_047424439.1	c.*9359A>G		3_prime_UTR_variant	3/3		XP_047280395.1
H4C15	XM_047424442.1	c.*8965A>G		3_prime_UTR_variant	3/3		XP_047280398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000290792	ENST00000564237.2	n.4997A>G		non_coding_transcript_exon_variant	1/1	6
ENSG00000290791	ENST00000608318.2	n.3067T>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7595 AN: 152140 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.0499 AC: 7595 AN: 152258 Hom.: 252 Cov.: 32 AF XY: 0.0479 AC XY: 3566 AN XY: 74436

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00974

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0680 Hom.: 125

Bravo AF: 0.0465

Asia WGS AF: 0.00635 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1046332; hg19: chr1-149817508;