rs260964

chr1-39092100-T-Cchr1-39092100-T-G

Variant summary

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

The ENST00000567887.5(MACF1):c.220+7662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,058 control chromosomes in the GnomAD database, including 36,853 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 0.69 (36853 hom., cov: 31)
• Consequence: MACF1 ENST00000567887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACF1	NM_012090.5	c.220+7662T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACF1	ENST00000361689.7	c.220+7662T>C		intron_variant		5
MACF1	ENST00000372915.8	c.220+7662T>C		intron_variant		5		P1
MACF1	ENST00000484793.5	c.220+7662T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104317 AN: 151940 Hom.: 36831 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.686 AC: 104380 AN: 152058 Hom.: 36853 Cov.: 31 AF XY: 0.694 AC XY: 51578 AN XY: 74336

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.717

Alfa AF: 0.726 Hom.: 52753

Bravo AF: 0.682

Asia WGS AF: 0.892 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.2
Dann	Benign	0.67

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: rs260964; hg19: chr1-39557772; COSMIC: COSV58365621;