1-39084466-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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 1-39084466-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 GnomAd at 316 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_012090.5	c.220+28C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000361689.7	c.220+28C>T		intron_variant		5
MACF1	ENST00000372915.8	c.220+28C>T		intron_variant		5		P1
MACF1	ENST00000484793.5	c.220+28C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00208 AC: 316 AN: 152150 Hom.: 13 Cov.: 32

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.: 26 AF XY: 0.00403 AC XY: 467 AN XY: 115836

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.: 48 Cov.: 30 AF XY: 0.00128 AC XY: 911 AN XY: 711500

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.: 13 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74458

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.: 2

Bravo AF: 0.00238

Asia WGS AF: 0.0160 AC: 55 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 21, 2021

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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

Other links and lift over

dbSNP: rs117942915; hg19: chr1-39550138; COSMIC: COSV58376386;