1-39344315-T-C

Position:

• chr1-39344315-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394062.1(MACF1):​c.10582-2662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 151,210 control chromosomes in the GnomAD database, including 66,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (66504 hom., cov: 25)
• Consequence: MACF1 NM_001394062.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACF1	NM_001394062.1	c.10582-2662T>C		intron_variant		ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5	c.4630-5163T>C		intron_variant			NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6	c.10582-2662T>C		intron_variant		5	NM_001394062.1	ENSP00000455274

Frequencies

GnomAD3 genomes AF: 0.937 AC: 141509 AN: 151092 Hom.: 66471 Cov.: 25

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.939

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.936 AC: 141593 AN: 151210 Hom.: 66504 Cov.: 25 AF XY: 0.937 AC XY: 69170 AN XY: 73848

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.956

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.931

Alfa AF: 0.955 Hom.: 8104

Bravo AF: 0.930

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.65

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: rs7528276; hg19: chr1-39809987;