1-39231046-C-A

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.110-136C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 718,232 control chromosomes in the GnomAD database, including 623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (239 hom., cov: 32)
  • Exomes 𝑓: 0.030 (384 hom.)
• Consequence: MACF1 NM_001394062.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-39231046-C-A is Benign according to our data. Variant chr1-39231046-C-A is described in ClinVar as [Benign]. Clinvar id is 1280302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_001394062.1	c.110-136C>A		intron_variant		ENST00000564288.6
MACF1	NM_012090.5	c.221-136C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000564288.6	c.110-136C>A		intron_variant		5	NM_001394062.1
	ENST00000669616.1	n.75-2510G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7081 AN: 152160 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0300 AC: 16992 AN: 565956 Hom.: 384 AF XY: 0.0307 AC XY: 9297 AN XY: 302896

Gnomad4 AFR exome AF: 0.0960

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0237

Gnomad4 EAS exome AF: 0.000114

Gnomad4 SAS exome AF: 0.0533

Gnomad4 FIN exome AF: 0.0324

Gnomad4 NFE exome AF: 0.0271

Gnomad4 OTH exome AF: 0.0307

GnomAD4 genome AF: 0.0466 AC: 7096 AN: 152276 Hom.: 239 Cov.: 32 AF XY: 0.0467 AC XY: 3476 AN XY: 74470

Gnomad4 AFR AF: 0.0937

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0568

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0145 Hom.: 5

Bravo AF: 0.0478

Asia WGS AF: 0.0380 AC: 133 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 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	12
Dann	Benign	0.82

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: rs1932507; hg19: chr1-39696718;