rs34966100

Variant names:

• chr6-26031734-G-A
• rs34966100
• NM_003537.4:c.327C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-26031734-G-A
• chr6-26031734-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003537.4(H3C2):​c.327C>T​(p.Asn109Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00935 in 1,614,190 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (216 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (200 hom.)
• Consequence: H3C2 NM_003537.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.54
• Publications: 4 publications found

Genes affected

H3C2 (HGNC:4776): (H3 clustered histone 2) 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 is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-26031734-G-A is Benign according to our data. Variant chr6-26031734-G-A is described in ClinVar as Benign. ClinVar VariationId is 873165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003537.4. 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
	H3C2	NM_003537.4	MANE Select	c.327C>T	p.Asn109Asn	synonymous	Exon 1 of 1	NP_003528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H3C2	ENST00000621411.3	TSL:6 MANE Select	c.327C>T	p.Asn109Asn	synonymous	Exon 1 of 1	ENSP00000484841.2	P68431
	LINC02980	ENST00000730115.1		n.562-9598G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4710 AN: 152190 Hom.: 216 Cov.: 33

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00509

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.0113 AC: 2837 AN: 251484 AF XY: 0.00927

Gnomad AFR exome AF: 0.0981

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00261

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00461

Gnomad OTH exome AF: 0.00912

GnomAD4 exome AF: 0.00710 AC: 10377 AN: 1461882 Hom.: 200 Cov.: 34 AF XY: 0.00660 AC XY: 4800 AN XY: 727244

African (AFR) AF: 0.0984 AC: 3295 AN: 33478

American (AMR) AF: 0.0135 AC: 602 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00413 AC: 108 AN: 26136

East Asian (EAS) AF: 0.00171 AC: 68 AN: 39700

South Asian (SAS) AF: 0.00539 AC: 465 AN: 86258

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53420

Middle Eastern (MID) AF: 0.0107 AC: 62 AN: 5768

European-Non Finnish (NFE) AF: 0.00461 AC: 5131 AN: 1112004

Other (OTH) AF: 0.0103 AC: 621 AN: 60396

GnomAD4 genome AF: 0.0310 AC: 4714 AN: 152308 Hom.: 216 Cov.: 33 AF XY: 0.0296 AC XY: 2207 AN XY: 74486

African (AFR) AF: 0.0949 AC: 3943 AN: 41566

American (AMR) AF: 0.0208 AC: 319 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00509 AC: 346 AN: 68014

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.0163 Hom.: 61

Bravo AF: 0.0371

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00492

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Squamous cell lung carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.6
DANN	Benign	0.91
PhyloP100		5.5
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34966100; hg19: chr6-26031962; COSMIC: COSV106370362; COSMIC: COSV106370362;