Variant chr1-39084245-C-CAGTGAGCGGTCATGTCGGAGTGAGCGGTCATGTCGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The ENST00000567887.5(MACF1):c.56_57insATGTCGGAGTGAGCGGTCATGTCGGAGTGAGCGGTC(p.Cys14_Ser25dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.0000788 in 152,292 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

MACF1
ENST00000567887.5 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.44

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in ENST00000567887.5.

BP6

Variant 1-39084245-C-CAGTGAGCGGTCATGTCGGAGTGAGCGGTCATGTCGG is Benign according to our data. Variant chr1-39084245-C-CAGTGAGCGGTCATGTCGGAGTGAGCGGTCATGTCGG is described in ClinVar as [Benign]. Clinvar id is 2053003.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000788 (12/152292) while in subpopulation AMR AF= 0.000784 (12/15298). AF 95% confidence interval is 0.000452. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACF1	NM_012090.5 linkuse as main transcript	c.56_57insATGTCGGAGTGAGCGGTCATGTCGGAGTGAGCGGTC	p.Cys14_Ser25dup	inframe_insertion	1/93		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris	UniProt
MACF1	ENST00000361689.7 linkuse as main transcript	c.56_57insATGTCGGAGTGAGCGGTCATGTCGGAGTGAGCGGTC	p.Cys14_Ser25dup	inframe_insertion	2/94	5	ENSP00000354573		Q9UPN3-2
MACF1	ENST00000372915.8 linkuse as main transcript	c.56_57insATGTCGGAGTGAGCGGTCATGTCGGAGTGAGCGGTC	p.Cys14_Ser25dup	inframe_insertion	1/96	5	ENSP00000362006	P1
MACF1	ENST00000484793.5 linkuse as main transcript	c.56_57insATGTCGGAGTGAGCGGTCATGTCGGAGTGAGCGGTC	p.Cys14_Ser25dup	inframe_insertion	3/4	2	ENSP00000434859

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000749

AC:

188

AN:

250904

Hom.:

AF XY:

0.000545

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00532

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000119

AC:

174

AN:

1460922

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00381

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2023

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over