1-39453562-A-G

Position:

• chr1-39453562-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394062.1(MACF1):​c.20743-145A>G variant causes a intron change. The variant allele was found at a frequency of 0.543 in 675,280 control chromosomes in the GnomAD database, including 102,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24310 hom., cov: 32)
  • Exomes 𝑓: 0.54 (78001 hom.)
• Consequence: MACF1 NM_001394062.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.63

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-39453562-A-G is Benign according to our data. Variant chr1-39453562-A-G is described in ClinVar as [Benign]. Clinvar id is 1291665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACF1	NM_001394062.1	c.20743-145A>G		intron_variant		ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5	c.14566-145A>G		intron_variant			NP_036222.3
MACF1	NM_001397473.1	c.8821-145A>G		intron_variant			NP_001384402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6	c.20743-145A>G		intron_variant		5	NM_001394062.1	ENSP00000455274.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85200 AN: 152010 Hom.: 24285 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.538 AC: 281358 AN: 523152 Hom.: 78001 AF XY: 0.529 AC XY: 144426 AN XY: 272944

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.561 AC: 85269 AN: 152128 Hom.: 24310 Cov.: 32 AF XY: 0.553 AC XY: 41122 AN XY: 74366

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.565

Alfa AF: 0.560 Hom.: 51887

Bravo AF: 0.560

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs687848; hg19: chr1-39919234;