chr1-1045067-T-G

Variant names:

• chr1-1045067-T-G
• rs189331845
• NM_198576.4:c.2255-94T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198576.4(AGRN):​c.2255-94T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,367,374 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000072 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000098 (1 hom.)
• Consequence: AGRN NM_198576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

Genes affected

AGRN (HGNC:329): (agrin) This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4	c.2255-94T>G		intron_variant	Intron 12 of 35	ENST00000379370.7	NP_940978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGRN	ENST00000379370.7	c.2255-94T>G		intron_variant	Intron 12 of 35	1	NM_198576.4	ENSP00000368678.2
AGRN	ENST00000651234.1	c.1940-94T>G		intron_variant	Intron 11 of 37			ENSP00000499046.1
AGRN	ENST00000652369.2	c.1940-94T>G		intron_variant	Intron 11 of 34			ENSP00000498543.1
AGRN	ENST00000620552.4	c.1841-94T>G		intron_variant	Intron 12 of 38	5		ENSP00000484607.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151996 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000979 AC: 119 AN: 1215260 Hom.: 1 AF XY: 0.0000797 AC XY: 49 AN XY: 614556

African (AFR) AF: 0.00 AC: 0 AN: 28512

American (AMR) AF: 0.00 AC: 0 AN: 44056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24370

East Asian (EAS) AF: 0.00284 AC: 109 AN: 38330

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3682

European-Non Finnish (NFE) AF: 0.00000224 AC: 2 AN: 891982

Other (OTH) AF: 0.000115 AC: 6 AN: 52050

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152114 Hom.: 1 Cov.: 33 AF XY: 0.0000941 AC XY: 7 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41490

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000174

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.35
DANN	Benign	0.54
PhyloP100		-0.38

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

Publications

Loading publications...

Other links and lift over

dbSNP: rs189331845; hg19: chr1-980447;