11-94544295-A-C

Variant names:

• chr11-94544295-A-C
• rs190868751
• NM_002033.4:c.162A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002033.4(FUT4):​c.162A>C​(p.Pro54Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,563,300 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (32 hom.)
• Consequence: FUT4 NM_002033.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.45
• Publications: 0 publications found

Genes affected

FUT4 (HGNC:4015): (fucosyltransferase 4) The product of this gene transfers fucose to N-acetyllactosamine polysaccharides to generate fucosylated carbohydrate structures. It catalyzes the synthesis of the non-sialylated antigen, Lewis x (CD15). [provided by RefSeq, Jan 2009]

PIWIL4 (HGNC:18444): (piwi like RNA-mediated gene silencing 4) PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

ENSG00000304830 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-94544295-A-C is Benign according to our data. Variant chr11-94544295-A-C is described in ClinVar as [Benign]. Clinvar id is 776650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.45 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT4	NM_002033.4	c.162A>C	p.Pro54Pro	synonymous_variant	Exon 1 of 1	ENST00000358752.4	NP_002024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT4	ENST00000358752.4	c.162A>C	p.Pro54Pro	synonymous_variant	Exon 1 of 1	6	NM_002033.4	ENSP00000351602.2
PIWIL4	ENST00000543336.5	n.-121+306A>C		intron_variant	Intron 1 of 13	2		ENSP00000444575.1
ENSG00000304830	ENST00000806516.1	n.-151T>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2010 AN: 152110 Hom.: 46 Cov.: 33

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00183 AC: 321 AN: 175146 AF XY: 0.00136

Gnomad AFR exome AF: 0.0398

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.000384

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000242

GnomAD4 exome AF: 0.00133 AC: 1878 AN: 1411082 Hom.: 32 Cov.: 31 AF XY: 0.00118 AC XY: 828 AN XY: 700770

African (AFR) AF: 0.0527 AC: 1527 AN: 28964

American (AMR) AF: 0.00216 AC: 88 AN: 40786

Ashkenazi Jewish (ASJ) AF: 0.0000814 AC: 2 AN: 24582

East Asian (EAS) AF: 0.00 AC: 0 AN: 33908

South Asian (SAS) AF: 0.000110 AC: 9 AN: 81978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46306

Middle Eastern (MID) AF: 0.00231 AC: 10 AN: 4338

European-Non Finnish (NFE) AF: 0.0000613 AC: 67 AN: 1092148

Other (OTH) AF: 0.00301 AC: 175 AN: 58072

GnomAD4 genome AF: 0.0133 AC: 2021 AN: 152218 Hom.: 47 Cov.: 33 AF XY: 0.0128 AC XY: 955 AN XY: 74420

African (AFR) AF: 0.0461 AC: 1917 AN: 41554

American (AMR) AF: 0.00490 AC: 75 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

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

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67978

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00822 Hom.: 3

Bravo AF: 0.0160

Asia WGS AF: 0.00550 AC: 19 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-5.4
PromoterAI		0.045	Neutral
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: rs190868751; hg19: chr11-94277461;