1-39092100-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000567887.5(MACF1):​c.220+7662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,058 control chromosomes in the GnomAD database, including 36,853 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 0.69 ( 36853 hom., cov: 31)

Consequence

MACF1
ENST00000567887.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.661

Publications

2 publications found
Variant links:
Genes affected
MACF1 (HGNC:13664): (microtubule actin crosslinking factor 1) This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]
MACF1 Gene-Disease associations (from GenCC):
  • lissencephaly 9 with complex brainstem malformation
    Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics
  • lissencephaly spectrum disorder with complex brainstem malformation
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen
  • autosomal dominant nonsyndromic hearing loss
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MACF1NM_012090.5 linkc.220+7662T>C intron_variant Intron 1 of 92 NP_036222.3 Q9UPN3-2Q6ZSD7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MACF1ENST00000567887.5 linkc.220+7662T>C intron_variant Intron 1 of 100 5 ENSP00000455823.1 H3BQK9
MACF1ENST00000372915.8 linkc.220+7662T>C intron_variant Intron 1 of 95 5 ENSP00000362006.4 A0A7P0MQR8
MACF1ENST00000361689.7 linkc.220+7662T>C intron_variant Intron 2 of 93 5 ENSP00000354573.2 Q9UPN3-2

Frequencies

GnomAD3 genomes
AF:
0.687
AC:
104317
AN:
151940
Hom.:
36831
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.520
Gnomad AMI
AF:
0.547
Gnomad AMR
AF:
0.778
Gnomad ASJ
AF:
0.718
Gnomad EAS
AF:
0.991
Gnomad SAS
AF:
0.838
Gnomad FIN
AF:
0.739
Gnomad MID
AF:
0.750
Gnomad NFE
AF:
0.724
Gnomad OTH
AF:
0.714
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.686
AC:
104380
AN:
152058
Hom.:
36853
Cov.:
31
AF XY:
0.694
AC XY:
51578
AN XY:
74336
show subpopulations
African (AFR)
AF:
0.519
AC:
21524
AN:
41438
American (AMR)
AF:
0.779
AC:
11902
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.718
AC:
2486
AN:
3464
East Asian (EAS)
AF:
0.991
AC:
5130
AN:
5176
South Asian (SAS)
AF:
0.838
AC:
4034
AN:
4816
European-Finnish (FIN)
AF:
0.739
AC:
7814
AN:
10572
Middle Eastern (MID)
AF:
0.738
AC:
217
AN:
294
European-Non Finnish (NFE)
AF:
0.724
AC:
49260
AN:
67992
Other (OTH)
AF:
0.717
AC:
1515
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1609
3218
4826
6435
8044
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
824
1648
2472
3296
4120
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.720
Hom.:
65642
Bravo
AF:
0.682
Asia WGS
AF:
0.892
AC:
3100
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.2
DANN
Benign
0.67
PhyloP100
-0.66
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

Publications

Other links and lift over

dbSNP: rs260964; hg19: chr1-39557772; COSMIC: COSV58365621; API