chr1-226068253-G-A

Variant names:

• chr1-226068253-G-A
• rs6664668
• NM_002107.7:c.282+2444G>A

Variant summary

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

The NM_002107.7(H3-3A):​c.282+2444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 152,224 control chromosomes in the GnomAD database, including 69,885 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 0.96 (69885 hom., cov: 31)
• Consequence: H3-3A NM_002107.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 1 publications found

Genes affected

H3-3A (HGNC:4764): (H3.3 histone A) 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 contains introns and its mRNA is polyadenylated, unlike most histone genes. The protein encoded is a replication-independent member of the histone H3 family. [provided by RefSeq, Jul 2008]

H3-3A Gene-Disease associations (from GenCC):

• Bryant-Li-Bhoj neurodevelopmental syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H3-3A	NM_002107.7	c.282+2444G>A		intron_variant	Intron 3 of 3	ENST00000366815.10	NP_002098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H3-3A	ENST00000366815.10	c.282+2444G>A		intron_variant	Intron 3 of 3	1	NM_002107.7	ENSP00000355780.3

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145383 AN: 152106 Hom.: 69846 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.977

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

GnomAD4 genome AF: 0.956 AC: 145481 AN: 152224 Hom.: 69885 Cov.: 31 AF XY: 0.956 AC XY: 71186 AN XY: 74424

African (AFR) AF: 0.847 AC: 35136 AN: 41482

American (AMR) AF: 0.980 AC: 14992 AN: 15296

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5172

South Asian (SAS) AF: 0.999 AC: 4823 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67999 AN: 68038

Other (OTH) AF: 0.977 AC: 2066 AN: 2114

Alfa AF: 0.983 Hom.: 74830

Bravo AF: 0.948

Asia WGS AF: 0.990 AC: 3445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.55
PhyloP100		-0.036
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: rs6664668; hg19: chr1-226255954;