Variant chr1-39084466-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000567887.5(MACF1):c.220+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,583,426 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 48 hom. )

Consequence

MACF1
ENST00000567887.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-39084466-C-T is Benign according to our data. Variant chr1-39084466-C-T is described in ClinVar as [Benign]. Clinvar id is 1279892.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0021 (320/152268) while in subpopulation EAS AF= 0.05 (259/5180). AF 95% confidence interval is 0.045. There are 13 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 320 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACF1	NM_012090.5 linkuse as main transcript	c.220+28C>T		intron_variant			NP_036222.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris	UniProt
MACF1	ENST00000361689.7 linkuse as main transcript	c.220+28C>T	intron_variant	5	ENSP00000354573		Q9UPN3-2
MACF1	ENST00000372915.8 linkuse as main transcript	c.220+28C>T	intron_variant	5	ENSP00000362006	P1
MACF1	ENST00000484793.5 linkuse as main transcript	c.220+28C>T	intron_variant	2	ENSP00000434859

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0497

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00451

AC:

955

AN:

211590

Hom.:

AF XY:

0.00403

AC XY:

467

AN XY:

115836

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.0000947

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0557

Gnomad SAS exome

AF:

0.000884

Gnomad FIN exome

AF:

0.0000839

Gnomad NFE exome

AF:

0.0000835

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00134

AC:

1924

AN:

1431158

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

911

AN XY:

711500

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.000141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0390

Gnomad4 SAS exome

AF:

0.000829

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000773

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.00210

AC:

320

AN:

152268

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0500

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.00238

Asia WGS

AF:

0.0160

AC:

AN:

3478

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

GeneDx

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

DANN

Benign

0.61

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

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