1-39084589-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+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 708,664 control chromosomes in the GnomAD database, including 5,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1006 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4389 hom.)
• Consequence: MACF1 ENST00000567887.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280

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=-0.9).
• BP6: Variant 1-39084589-C-T is Benign according to our data. Variant chr1-39084589-C-T is described in ClinVar as [Benign]. Clinvar id is 1181179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_012090.5	c.220+151C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000361689.7	c.220+151C>T		intron_variant		5
MACF1	ENST00000372915.8	c.220+151C>T		intron_variant		5		P1
MACF1	ENST00000484793.5	c.220+151C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16210 AN: 152070 Hom.: 1004 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.116 AC: 64768 AN: 556474 Hom.: 4389 AF XY: 0.114 AC XY: 32709 AN XY: 287070

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0653

Gnomad4 SAS exome AF: 0.0816

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.107 AC: 16220 AN: 152190 Hom.: 1006 Cov.: 32 AF XY: 0.109 AC XY: 8079 AN XY: 74412

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.0609

Gnomad4 SAS AF: 0.0688

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.123 Hom.: 233

Bravo AF: 0.0994

Asia WGS AF: 0.0630 AC: 218 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	-0.90
Cadd	Benign	6.4
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: rs76104968; hg19: chr1-39550261;