rs16841344

chr1-228462027-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000620438.2(H2BC26):c.*3517T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 152,528 control chromosomes in the GnomAD database, including 54 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 0.021 (51 hom., cov: 31)
  • Exomes 𝑓: 0.034 (3 hom.)
• Consequence: H2BC26 ENST00000620438.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

H2BC26 (HGNC:20514): (H2B clustered histone 26) 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 is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. Transcripts from this gene contain a palindromic termination element. [provided by RefSeq, Aug 2015]

MIR4666A (HGNC:41750): (microRNA 4666a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0214 (3227/150448) while in subpopulation EAS AF= 0.0447 (219/4902). AF 95% confidence interval is 0.0398. There are 51 homozygotes in gnomad4. There are 1609 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 52 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR4666A	NR_039812.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H2BC26	ENST00000620438.2	c.*3517T>A		3_prime_UTR_variant	1/1			P1
H2BC26	ENST00000690378.1	n.1161T>A		non_coding_transcript_exon_variant	2/2
MIR4666A	ENST00000580160.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3231 AN: 150328 Hom.: 52 Cov.: 31

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.0232

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0212

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.00603

Gnomad FIN AF: 0.00745

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00833 AC: 3 AN: 360 Hom.: 0 AF XY: 0.0147 AC XY: 3 AN XY: 204

Gnomad AFR exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00578

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0337 AC: 70 AN: 2080 Hom.: 3 Cov.: 0 AF XY: 0.0338 AC XY: 35 AN XY: 1036

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0116

Gnomad4 NFE exome AF: 0.00568

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0214 AC: 3227 AN: 150448 Hom.: 51 Cov.: 31 AF XY: 0.0219 AC XY: 1609 AN XY: 73480

Gnomad4 AFR AF: 0.0338

Gnomad4 AMR AF: 0.0381

Gnomad4 ASJ AF: 0.0212

Gnomad4 EAS AF: 0.0447

Gnomad4 SAS AF: 0.00603

Gnomad4 FIN AF: 0.00745

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.0163 Hom.: 6

Bravo AF: 0.0262

Asia WGS AF: 0.0310 AC: 107 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	0.23
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16841344; hg19: chr1-228649728;