11-373061-C-T

Variant names:

• chr11-373061-C-T
• rs115266356
• NM_178537.5:c.480C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_178537.5(B4GALNT4):​c.480C>T​(p.Pro160Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,612,550 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (31 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (38 hom.)
• Consequence: B4GALNT4 NM_178537.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.621
• Publications: 0 publications found

Genes affected

B4GALNT4 (HGNC:26315): (beta-1,4-N-acetyl-galactosaminyltransferase 4) Enables acetylgalactosaminyltransferase activity. Predicted to be located in Golgi cisterna membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 11-373061-C-T is Benign according to our data. Variant chr11-373061-C-T is described in ClinVar as [Benign]. Clinvar id is 713985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.621 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1666/152114) while in subpopulation AFR AF = 0.038 (1575/41488). AF 95% confidence interval is 0.0364. There are 31 homozygotes in GnomAd4. There are 719 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1666 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT4	NM_178537.5	c.480C>T	p.Pro160Pro	synonymous_variant	Exon 5 of 20	ENST00000329962.11	NP_848632.2
B4GALNT4	XM_017017654.2	c.204C>T	p.Pro68Pro	synonymous_variant	Exon 5 of 20		XP_016873143.1
B4GALNT4	XR_001747858.2	n.785C>T		non_coding_transcript_exon_variant	Exon 5 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT4	ENST00000329962.11	c.480C>T	p.Pro160Pro	synonymous_variant	Exon 5 of 20	1	NM_178537.5	ENSP00000328277.6

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1660 AN: 151996 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00292 AC: 729 AN: 250004 AF XY: 0.00199

Gnomad AFR exome AF: 0.0410

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00115 AC: 1682 AN: 1460436 Hom.: 38 Cov.: 38 AF XY: 0.000986 AC XY: 716 AN XY: 726510

African (AFR) AF: 0.0427 AC: 1428 AN: 33480

American (AMR) AF: 0.00197 AC: 88 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52096

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5764

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111920

Other (OTH) AF: 0.00200 AC: 121 AN: 60374

GnomAD4 genome AF: 0.0110 AC: 1666 AN: 152114 Hom.: 31 Cov.: 31 AF XY: 0.00967 AC XY: 719 AN XY: 74348

African (AFR) AF: 0.0380 AC: 1575 AN: 41488

American (AMR) AF: 0.00464 AC: 71 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67956

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00475 Hom.: 6

Bravo AF: 0.0126

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.41
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.62
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs115266356; hg19: chr11-373061;