NM_001004310.3:c.474C>T

Variant names:

• chr1-159809115-C-T
• rs148571854
• NM_001004310.3:c.474C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001004310.3(FCRL6):​c.474C>T​(p.Asp158Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,614,108 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (6 hom.)
• Consequence: FCRL6 NM_001004310.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115
• Publications: 0 publications found

Genes affected

FCRL6 (HGNC:31910): (Fc receptor like 6) Enables MHC class II protein binding activity and protein phosphatase binding activity. Predicted to be involved in cell surface receptor signaling pathway. Located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-159809115-C-T is Benign according to our data. Variant chr1-159809115-C-T is described in ClinVar as Benign. ClinVar VariationId is 717386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.115 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004310.3. 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
	FCRL6	NM_001004310.3	MANE Select	c.474C>T	p.Asp158Asp	synonymous	Exon 4 of 10	NP_001004310.2	Q6DN72-1
	FCRL6	NM_001426231.1		c.504C>T	p.Asp168Asp	synonymous	Exon 5 of 11	NP_001413160.1
	FCRL6	NM_001426232.1		c.495C>T	p.Asp165Asp	synonymous	Exon 5 of 11	NP_001413161.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL6	ENST00000368106.4	TSL:1 MANE Select	c.474C>T	p.Asp158Asp	synonymous	Exon 4 of 10	ENSP00000357086.3	Q6DN72-1
	FCRL6	ENST00000339348.9	TSL:1	c.474C>T	p.Asp158Asp	synonymous	Exon 4 of 9	ENSP00000340949.5	Q6DN72-3
	FCRL6	ENST00000392235.7	TSL:1	c.320-287C>T		intron	N/A	ENSP00000376068.3	Q6DN72-4

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00224

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000883 AC: 222 AN: 251296 AF XY: 0.000965

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00178

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00227 AC: 3314 AN: 1461818 Hom.: 6 Cov.: 33 AF XY: 0.00216 AC XY: 1574 AN XY: 727228

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00281 AC: 3130 AN: 1111966

Other (OTH) AF: 0.00257 AC: 155 AN: 60394

GnomAD4 genome AF: 0.00117 AC: 178 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74468

African (AFR) AF: 0.000529 AC: 22 AN: 41566

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00224 AC: 152 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00118

EpiCase AF: 0.00153

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.23
PhyloP100		0.12
Mutation Taster		=100/0	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: rs148571854; hg19: chr1-159778905;