rs838138

Variant names:

• chr19-48750460-G-T
• rs838138
• NM_001384359.1:c.822C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001384359.1(FUT1):​c.822C>A​(p.Thr274Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,614,156 control chromosomes in the GnomAD database, including 1,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.046 (521 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (501 hom.)
• Consequence: FUT1 NM_001384359.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0970
• Publications: 4 publications found

Genes affected

FUT1 (HGNC:4012): (fucosyltransferase 1 (H blood group)) This gene encodes a Golgi stack membrane protein that is involved in the creation of a precursor of the H antigen, which is required for the final step in the synthesis of soluble A and B antigens. This is one of two genes encoding the galactoside 2-L-fucosyltransferase enzyme. Mutations in this gene are a cause of the H-Bombay blood group. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-48750460-G-T is Benign according to our data. Variant chr19-48750460-G-T is described in ClinVar as Benign. ClinVar VariationId is 3055812.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.097 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384359.1. 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
	FUT1	NM_001384359.1	MANE Select	c.822C>A	p.Thr274Thr	synonymous	Exon 2 of 2	NP_001371288.1	Q6IZA2
	FUT1	NM_000148.4		c.822C>A	p.Thr274Thr	synonymous	Exon 4 of 4	NP_000139.1	P19526
	FUT1	NM_001329877.1		c.822C>A	p.Thr274Thr	synonymous	Exon 5 of 5	NP_001316806.1	Q6IZA2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT1	ENST00000645652.2	MANE Select	c.822C>A	p.Thr274Thr	synonymous	Exon 2 of 2	ENSP00000494643.1	P19526
	FUT1	ENST00000927212.1		c.822C>A	p.Thr274Thr	synonymous	Exon 2 of 2	ENSP00000597271.1
	FUT1	ENST00000927213.1		c.822C>A	p.Thr274Thr	synonymous	Exon 2 of 2	ENSP00000597272.1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6948 AN: 152166 Hom.: 519 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0315

GnomAD2 exomes AF: 0.0121 AC: 3044 AN: 251456 AF XY: 0.00898

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.00818

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00470 AC: 6875 AN: 1461872 Hom.: 501 Cov.: 33 AF XY: 0.00402 AC XY: 2925 AN XY: 727232

African (AFR) AF: 0.167 AC: 5597 AN: 33480

American (AMR) AF: 0.00930 AC: 416 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000612 AC: 16 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.000190 AC: 211 AN: 1112012

Other (OTH) AF: 0.00960 AC: 580 AN: 60396

GnomAD4 genome AF: 0.0458 AC: 6971 AN: 152284 Hom.: 521 Cov.: 33 AF XY: 0.0446 AC XY: 3322 AN XY: 74454

African (AFR) AF: 0.159 AC: 6586 AN: 41538

American (AMR) AF: 0.0187 AC: 286 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68030

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0256 Hom.: 180

Bravo AF: 0.0534

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FUT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.72
DANN	Benign	0.72
PhyloP100		-0.097
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

Other links and lift over

dbSNP: rs838138; hg19: chr19-49253717;