rs11616065

Variant names:

• chr12-57628241-G-A
• rs11616065
• NM_001478.5:c.1024C>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_001478.5(B4GALNT1):​c.1024C>T​(p.Leu342Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00899 in 1,614,272 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (16 hom., cov: 33)
  • Exomes 𝑓: 0.0092 (74 hom.)
• Consequence: B4GALNT1 NM_001478.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.27
• Publications: 5 publications found

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

B4GALNT1 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 26

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 12-57628241-G-A is Benign according to our data. Variant chr12-57628241-G-A is described in ClinVar as Benign. ClinVar VariationId is 413846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00732 (1115/152392) while in subpopulation NFE AF = 0.0109 (739/68046). AF 95% confidence interval is 0.0102. There are 16 homozygotes in GnomAd4. There are 502 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001478.5. 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
	B4GALNT1	NM_001478.5	MANE Select	c.1024C>T	p.Leu342Leu	synonymous	Exon 9 of 11	NP_001469.1	Q00973-1
	B4GALNT1	NM_001413967.1		c.1159C>T	p.Leu387Leu	synonymous	Exon 9 of 11	NP_001400896.1
	B4GALNT1	NM_001413968.1		c.1159C>T	p.Leu387Leu	synonymous	Exon 9 of 11	NP_001400897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.1024C>T	p.Leu342Leu	synonymous	Exon 9 of 11	ENSP00000341562.4	Q00973-1
	B4GALNT1	ENST00000882412.1		c.1159C>T	p.Leu387Leu	synonymous	Exon 9 of 11	ENSP00000552471.1
	B4GALNT1	ENST00000954202.1		c.1024C>T	p.Leu342Leu	synonymous	Exon 8 of 10	ENSP00000624261.1

Frequencies

GnomAD3 genomes AF: 0.00732 AC: 1115 AN: 152274 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00207

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00762 AC: 1916 AN: 251450 AF XY: 0.00795

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00639

Gnomad ASJ exome AF: 0.0125

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.00917 AC: 13401 AN: 1461880 Hom.: 74 Cov.: 32 AF XY: 0.00917 AC XY: 6668 AN XY: 727240

African (AFR) AF: 0.00137 AC: 46 AN: 33480

American (AMR) AF: 0.00642 AC: 287 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0137 AC: 358 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00633 AC: 546 AN: 86258

European-Finnish (FIN) AF: 0.00198 AC: 106 AN: 53410

Middle Eastern (MID) AF: 0.0196 AC: 113 AN: 5768

European-Non Finnish (NFE) AF: 0.0102 AC: 11390 AN: 1112008

Other (OTH) AF: 0.00916 AC: 553 AN: 60396

GnomAD4 genome AF: 0.00732 AC: 1115 AN: 152392 Hom.: 16 Cov.: 33 AF XY: 0.00674 AC XY: 502 AN XY: 74520

African (AFR) AF: 0.00207 AC: 86 AN: 41600

American (AMR) AF: 0.00392 AC: 60 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4828

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10628

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 739 AN: 68046

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00840 Hom.: 7

Bravo AF: 0.00829

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0117

EpiControl AF: 0.0126

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.9
DANN	Benign	0.90
PhyloP100		3.3
PromoterAI		0.095	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: rs11616065; hg19: chr12-58022024; COSMIC: COSV100247381; COSMIC: COSV100247381;