11-94544241-C-A

Variant names:

• chr11-94544241-C-A
• rs1194459555
• NM_002033.4:c.108C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002033.4(FUT4):​c.108C>A​(p.Gly36Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G36G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: FUT4 NM_002033.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.038 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT4	NM_002033.4	c.108C>A	p.Gly36Gly	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.108C>A	p.Gly36Gly	synonymous_variant	Exon 1 of 1	6	NM_002033.4	ENSP00000351602.2
PIWIL4	ENST00000543336.5	n.-121+252C>A		intron_variant	Intron 1 of 13	2		ENSP00000444575.1
ENSG00000304830	ENST00000806516.1	n.-97G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344646 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 662648

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

African (AFR) AF: 0.00 AC: 0 AN: 26928

American (AMR) AF: 0.00 AC: 0 AN: 28530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20496

East Asian (EAS) AF: 0.00 AC: 0 AN: 31648

South Asian (SAS) AF: 0.00 AC: 0 AN: 70824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3848

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060732

Other (OTH) AF: 0.00 AC: 0 AN: 54784

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.6
DANN	Benign	0.89
PhyloP100		-0.038
PromoterAI		-0.098	Neutral

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: rs1194459555; hg19: chr11-94277407;