rs587645491

Variant names:

• chr1-149791461-AAAG-A
• rs587645491
• NM_000566.4:c.1075_1077delGAA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_000566.4(FCGR1A):​c.1075_1077delGAA​(p.Glu359del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,608,606 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 26)
  • Exomes 𝑓: 0.00044 (6 hom.)
• Consequence: FCGR1A NM_000566.4 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.173
• Publications: 0 publications found

Genes affected

FCGR1A (HGNC:3613): (Fc gamma receptor Ia) This gene encodes a protein that plays an important role in the immune response. This protein is a high-affinity Fc-gamma receptor. The gene is one of three related gene family members located on chromosome 1. [provided by RefSeq, Jul 2008]

ENSG00000233030 (HGNC:):

H2BC18 (HGNC:24700): (H2B clustered histone 18) 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 encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000566.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 1-149791461-AAAG-A is Benign according to our data. Variant chr1-149791461-AAAG-A is described in ClinVar as Benign. ClinVar VariationId is 734579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000566.4. 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
	FCGR1A	NM_000566.4	MANE Select	c.1075_1077delGAA	p.Glu359del	conservative_inframe_deletion	Exon 6 of 6	NP_000557.1	P12314-1
	FCGR1A	NM_001378804.1		c.1078_1080delGAA	p.Glu360del	conservative_inframe_deletion	Exon 6 of 6	NP_001365733.1
	FCGR1A	NM_001378805.1		c.1054_1056delGAA	p.Glu352del	conservative_inframe_deletion	Exon 5 of 5	NP_001365734.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR1A	ENST00000369168.5	TSL:1 MANE Select	c.1075_1077delGAA	p.Glu359del	conservative_inframe_deletion	Exon 6 of 6	ENSP00000358165.4	P12314-1
	ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+494_1063+496delCTT		intron	N/A
	FCGR1A	ENST00000964516.1		c.1165_1167delGAA	p.Glu389del	conservative_inframe_deletion	Exon 7 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 472 AN: 149780 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000889

Gnomad OTH AF: 0.00442

GnomAD2 exomes AF: 0.00130 AC: 96 AN: 73676 AF XY: 0.000969

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.000938

GnomAD4 exome AF: 0.000440 AC: 642 AN: 1458716 Hom.: 6 AF XY: 0.000376 AC XY: 273 AN XY: 725646

African (AFR) AF: 0.0115 AC: 381 AN: 33274

American (AMR) AF: 0.000762 AC: 34 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26038

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39654

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000727 AC: 3 AN: 4126

European-Non Finnish (NFE) AF: 0.000139 AC: 154 AN: 1111470

Other (OTH) AF: 0.00105 AC: 63 AN: 60130

GnomAD4 genome AF: 0.00315 AC: 472 AN: 149890 Hom.: 4 Cov.: 26 AF XY: 0.00302 AC XY: 221 AN XY: 73198

African (AFR) AF: 0.0109 AC: 440 AN: 40466

American (AMR) AF: 0.00112 AC: 17 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5052

South Asian (SAS) AF: 0.00 AC: 0 AN: 4672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000889 AC: 6 AN: 67470

Other (OTH) AF: 0.00437 AC: 9 AN: 2060

Alfa AF: 0.00256 Hom.: 0

Bravo AF: 0.00363

Asia WGS AF: 0.00937 AC: 32 AN: 3428

ClinVar

ClinVar submissions as Germline

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
PhyloP100		0.17
Mutation Taster		=90/10	polymorphism

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: rs587645491; hg19: chr1-149763017;