6-26026947-G-A

Variant names:

• chr6-26026947-G-A
• rs182575157
• NM_003544.3:c.306C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003544.3(H4C2):​c.306C>T​(p.Gly102Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,608,936 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (17 hom.)
• Consequence: H4C2 NM_003544.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.325
• Publications: 2 publications found

Genes affected

H4C2 (HGNC:4789): (H4 clustered histone 2) 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 is intronless and encodes a replication-dependent histone that is a member of the histone H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]

LINC02980 (HGNC:56046): (long intergenic non-protein coding RNA 2980)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-26026947-G-A is Benign according to our data. Variant chr6-26026947-G-A is described in ClinVar as Benign. ClinVar VariationId is 784494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.325 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003544.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H4C2	NM_003544.3	MANE Select	c.306C>T	p.Gly102Gly	synonymous	Exon 1 of 1	NP_003535.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H4C2	ENST00000377745.5	TSL:6 MANE Select	c.306C>T	p.Gly102Gly	synonymous	Exon 1 of 1	ENSP00000366974.2	P62805
	H4C2	ENST00000718258.1		c.306C>T	p.Gly102Gly	synonymous	Exon 1 of 1	ENSP00000520698.1	P62805
	LINC02980	ENST00000730115.1		n.562-14385G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00315 AC: 782 AN: 247928 AF XY: 0.00323

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000670

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00131

Gnomad NFE exome AF: 0.00420

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00429 AC: 6253 AN: 1456590 Hom.: 17 Cov.: 33 AF XY: 0.00424 AC XY: 3068 AN XY: 723998

African (AFR) AF: 0.000570 AC: 19 AN: 33334

American (AMR) AF: 0.000653 AC: 29 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25802

East Asian (EAS) AF: 0.0130 AC: 516 AN: 39626

South Asian (SAS) AF: 0.00137 AC: 117 AN: 85700

European-Finnish (FIN) AF: 0.00130 AC: 69 AN: 53252

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5742

European-Non Finnish (NFE) AF: 0.00477 AC: 5285 AN: 1108590

Other (OTH) AF: 0.00358 AC: 215 AN: 60108

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74504

African (AFR) AF: 0.000842 AC: 35 AN: 41578

American (AMR) AF: 0.00170 AC: 26 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00944 AC: 49 AN: 5190

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00373 AC: 254 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00306 Hom.: 3

Bravo AF: 0.00266

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.87
PhyloP100		-0.33
PromoterAI		0.048	Neutral
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs182575157; hg19: chr6-26027175;