rs7538300

Positions:

• chr1-39187092-C-A
• chr1-39187092-C-G
• chr1-39187092-C-T

Variant summary

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

The ENST00000567887.5(MACF1):​c.221-44090C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,106 control chromosomes in the GnomAD database, including 28,873 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 0.60 (28873 hom., cov: 29)
• Consequence: MACF1 ENST00000567887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_012090.5	c.221-44090C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000361689.7	c.221-44090C>A		intron_variant		5
MACF1	ENST00000372915.8	c.221-44090C>A		intron_variant		5		P1
MACF1	ENST00000524432.5	c.95-44090C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90164 AN: 150990 Hom.: 28875 Cov.: 29

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.597 AC: 90157 AN: 151106 Hom.: 28873 Cov.: 29 AF XY: 0.604 AC XY: 44554 AN XY: 73796

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.611

Alfa AF: 0.666 Hom.: 25786

Bravo AF: 0.578

Asia WGS AF: 0.644 AC: 2239 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.71

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: rs7538300; hg19: chr1-39652764;