1-39084538-C-T

Variant summary

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

The ENST00000567887.5(MACF1):c.220+100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 882,860 control chromosomes in the GnomAD database, including 412,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (58845 hom., cov: 31)
  • Exomes 𝑓: 0.98 (354018 hom.)
• Consequence: MACF1 ENST00000567887.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.107

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-39084538-C-T is Benign according to our data. Variant chr1-39084538-C-T is described in ClinVar as [Benign]. Clinvar id is 1258058.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_012090.5	c.220+100C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000361689.7	c.220+100C>T		intron_variant		5
MACF1	ENST00000372915.8	c.220+100C>T		intron_variant		5		P1
MACF1	ENST00000484793.5	c.220+100C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129046 AN: 152060 Hom.: 58829 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.887

GnomAD4 exome AF: 0.981 AC: 716527 AN: 730682 Hom.: 354018 AF XY: 0.983 AC XY: 369116 AN XY: 375366

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.959

Gnomad4 ASJ exome AF: 0.978

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.957

GnomAD4 genome AF: 0.848 AC: 129103 AN: 152178 Hom.: 58845 Cov.: 31 AF XY: 0.852 AC XY: 63434 AN XY: 74430

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.888

Alfa AF: 0.923 Hom.: 22432

Bravo AF: 0.826

Asia WGS AF: 0.971 AC: 3375 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.86
Dann	Benign	0.76

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: rs260972; hg19: chr1-39550210;