1-149784064-C-T

Variant names:

• chr1-149784064-C-T
• rs80039899
• NM_000566.4:c.114C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000566.4(FCGR1A):​c.114C>T​(p.Thr38Thr) 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]

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 -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 the male GnomAd4 subpopulation. Median coverage is 26. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR1A	NM_000566.4	c.114C>T	p.Thr38Thr	synonymous_variant	Exon 3 of 6	ENST00000369168.5	NP_000557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5	c.114C>T	p.Thr38Thr	synonymous_variant	Exon 3 of 6	1	NM_000566.4	ENSP00000358165.4

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

GnomAD2 exomes AF: 0.0106 AC: 2660 AN: 250440 AF XY: 0.0119

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 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 AC: 1616 AN: 33406

Gnomad4 AMR exome AF: 0.00421 AC: 188 AN: 44698

Gnomad4 ASJ exome AF: 0.00739 AC: 193 AN: 26132

Gnomad4 EAS exome AF: 0.0000504 AC: 2 AN: 39700

Gnomad4 SAS exome AF: 0.0410 AC: 3531 AN: 86162

Gnomad4 FIN exome AF: 0.00213 AC: 114 AN: 53404

Gnomad4 NFE exome AF: 0.00194 AC: 2154 AN: 1111824

Gnomad4 Remaining exome AF: 0.00772 AC: 465 AN: 60204

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 AC: 0.0466859 AN: 0.0466859

Gnomad4 AMR AF: 0.00533 AC: 0.00532684 AN: 0.00532684

Gnomad4 ASJ AF: 0.00893 AC: 0.00893372 AN: 0.00893372

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0352 AC: 0.0351759 AN: 0.0351759

Gnomad4 FIN AF: 0.000757 AC: 0.000757432 AN: 0.000757432

Gnomad4 NFE AF: 0.00274 AC: 0.00274005 AN: 0.00274005

Gnomad4 OTH AF: 0.0163 AC: 0.0162524 AN: 0.0162524

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs80039899; hg19: chr1-149755620;