NM_000566.4:c.21G>A

Variant names:

• chr1-149782764-G-A
• rs141598661
• NM_000566.4:c.21G>A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.856
• Publications: 1 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]

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]

LOC124904411 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.21G>A	p.Leu7Leu	synonymous	Exon 1 of 6	NP_000557.1	P12314-1
	FCGR1A	NM_001378804.1		c.21G>A	p.Leu7Leu	synonymous	Exon 1 of 6	NP_001365733.1
	FCGR1A	NM_001378805.1		c.21G>A	p.Leu7Leu	synonymous	Exon 1 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.21G>A	p.Leu7Leu	synonymous	Exon 1 of 6	ENSP00000358165.4	P12314-1
	FCGR1A	ENST00000964516.1		c.21G>A	p.Leu7Leu	synonymous	Exon 1 of 7	ENSP00000634575.1
	FCGR1A	ENST00000866776.1		c.21G>A	p.Leu7Leu	synonymous	Exon 1 of 6	ENSP00000536835.1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3354 AN: 146450 Hom.: 122 Cov.: 22

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

GnomAD2 exomes AF: 0.00461 AC: 835 AN: 181234 AF XY: 0.00350

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0869 AC: 2745 AN: 31598

American (AMR) AF: 0.00368 AC: 163 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.000807 AC: 21 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.000291 AC: 25 AN: 85794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00730 AC: 30 AN: 4110

European-Non Finnish (NFE) AF: 0.000220 AC: 243 AN: 1103048

Other (OTH) AF: 0.00635 AC: 379 AN: 59650

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0831 AC: 3173 AN: 38178

American (AMR) AF: 0.00768 AC: 114 AN: 14840

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4888

South Asian (SAS) AF: 0.000654 AC: 3 AN: 4590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10344

Middle Eastern (MID) AF: 0.0138 AC: 4 AN: 290

European-Non Finnish (NFE) AF: 0.000358 AC: 24 AN: 67072

Other (OTH) AF: 0.0191 AC: 39 AN: 2038

Alfa AF: 0.0156 Hom.: 9

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.5
DANN	Benign	0.69
PhyloP100		0.86
PromoterAI		-0.037	Neutral
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: rs141598661; hg19: chr1-149754320;