chr1-149782764-G-A

Position:

• chr1-149782764-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000566.4(FCGR1A):​c.21G>A​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (124 hom., cov: 22)
  • Exomes 𝑓: 0.0025 (134 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR1A NM_000566.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.856

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]

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]

FCGR1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-149782764-G-A is Benign according to our data. Variant chr1-149782764-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 769529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.856 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR1A	NM_000566.4	c.21G>A	p.Leu7Leu	synonymous_variant	1/6	ENST00000369168.5	NP_000557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5	c.21G>A	p.Leu7Leu	synonymous_variant	1/6	1	NM_000566.4	ENSP00000358165.4
FCGR1A	ENST00000444948.5	c.21G>A	p.Leu7Leu	synonymous_variant	1/4	2		ENSP00000394279.1
H2BC18	ENST00000545683	c.*469C>T		3_prime_UTR_variant	2/2	2		ENSP00000445831.1
FCGR1A	ENST00000489479.1	n.37G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3354 AN: 146450 Hom.: 122 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00769

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000871

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.000358

Gnomad OTH AF: 0.0193

GnomAD3 exomes AF: 0.00461 AC: 835 AN: 181234 Hom.: 34 AF XY: 0.00350 AC XY: 340 AN XY: 97156

Gnomad AFR exome AF: 0.0790

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000249

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000305

Gnomad OTH exome AF: 0.00355

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00249 AC: 3606 AN: 1447386 Hom.: 134 Cov.: 27 AF XY: 0.00221 AC XY: 1592 AN XY: 720282

Gnomad4 AFR exome AF: 0.0869

Gnomad4 AMR exome AF: 0.00368

Gnomad4 ASJ exome AF: 0.000807

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000291

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000220

Gnomad4 OTH exome AF: 0.00635

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0229 AC: 3358 AN: 146562 Hom.: 124 Cov.: 22 AF XY: 0.0223 AC XY: 1594 AN XY: 71384

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.00768

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000654

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000358

Gnomad4 OTH AF: 0.0191

Alfa AF: 0.0156 Hom.: 9

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.5
DANN	Benign	0.69

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: rs141598661; hg19: chr1-149754320;