rs4712961

Positions:

• chr6-25727106-C-G
• chr6-25727106-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_170610.3(H2BC1):​c.198C>G​(p.Ser66Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: H2BC1 NM_170610.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.97

Genes affected

H2BC1 (HGNC:18730): (H2B clustered histone 1) 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 testis/sperm-specific member of the histone H2B family. Transcripts from this gene contain a palindromic termination element. [provided by RefSeq, Aug 2015]

ENSG00000290217 (HGNC:):

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-5.97 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H2BC1	NM_170610.3	c.198C>G	p.Ser66Ser	synonymous_variant	1/1	ENST00000274764.5	NP_733759.1
SLC17A1	XM_017011201.3	c.*3-3313G>C		intron_variant			XP_016866690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H2BC1	ENST00000274764.5	c.198C>G	p.Ser66Ser	synonymous_variant	1/1	6	NM_170610.3	ENSP00000274764.3
ENSG00000290217	ENST00000703602.1	c.*50+8235C>G		intron_variant				ENSP00000515390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0020
DANN	Benign	0.45

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: rs4712961; hg19: chr6-25727334;