1-149784064-C-T

Position:

• chr1-149784064-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000566.4(FCGR1A):​c.114C>T​(p.Thr38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 1,610,810 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (41 hom., cov: 26)
  • Exomes 𝑓: 0.0057 (163 hom.)
• Consequence: FCGR1A NM_000566.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69

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]

LOC124904411 (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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-149784064-C-T is Benign according to our data. Variant chr1-149784064-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 790487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.016 (2423/151144) while in subpopulation AFR AF= 0.0467 (1906/40826). AF 95% confidence interval is 0.0449. There are 41 homozygotes in gnomad4. There are 1178 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR1A	NM_000566.4	c.114C>T	p.Thr38=	synonymous_variant	3/6	ENST00000369168.5	NP_000557.1
LOC124904411	XM_047438183.1	c.*577-804G>A		intron_variant			XP_047294139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5	c.114C>T	p.Thr38=	synonymous_variant	3/6	1	NM_000566.4	ENSP00000358165	P1
FCGR1A	ENST00000444948.5	c.31+1290C>T		intron_variant		2		ENSP00000394279
H2BC18	ENST00000545683.1	c.378-804G>A		intron_variant		2		ENSP00000445831
H2BC18	ENST00000420462.1	n.76-804G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2416 AN: 151028 Hom.: 41 Cov.: 26

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00533

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00274

Gnomad OTH AF: 0.0164

GnomAD3 exomes AF: 0.0106 AC: 2660 AN: 250440 Hom.: 61 AF XY: 0.0119 AC XY: 1607 AN XY: 135438

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.00374

Gnomad ASJ exome AF: 0.00874

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0412

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00324

Gnomad OTH exome AF: 0.00621

GnomAD4 exome AF: 0.00573 AC: 8362 AN: 1459666 Hom.: 163 Cov.: 31 AF XY: 0.00675 AC XY: 4904 AN XY: 726130

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.00421

Gnomad4 ASJ exome AF: 0.00739

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0410

Gnomad4 FIN exome AF: 0.00213

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.00772

GnomAD4 genome AF: 0.0160 AC: 2423 AN: 151144 Hom.: 41 Cov.: 26 AF XY: 0.0160 AC XY: 1178 AN XY: 73850

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.00533

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.000757

Gnomad4 NFE AF: 0.00274

Gnomad4 OTH AF: 0.0163

Alfa AF: 0.0111 Hom.: 3

Bravo AF: 0.0173

EpiCase AF: 0.00458

EpiControl AF: 0.00516

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 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.68

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: rs80039899; hg19: chr1-149755620;