rs582883

Variant names:

• chr1-39369868-T-C
• rs582883
• NM_001394062.1:c.12939-162T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394062.1(MACF1):​c.12939-162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,076 control chromosomes in the GnomAD database, including 11,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11150 hom., cov: 32)
• Consequence: MACF1 NM_001394062.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.232

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=-0.94).
• BP6: Variant 1-39369868-T-C is Benign according to our data. Variant chr1-39369868-T-C is described in ClinVar as [Benign]. Clinvar id is 1257453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_001394062.1	c.12939-162T>C		intron_variant	Intron 50 of 100	ENST00000564288.6	NP_001380991.1
MACF1	NM_012090.5	c.6753-162T>C		intron_variant	Intron 44 of 92		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000564288.6	c.12939-162T>C		intron_variant	Intron 50 of 100	5	NM_001394062.1	ENSP00000455274.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55448 AN: 151958 Hom.: 11116 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.365 AC: 55532 AN: 152076 Hom.: 11150 Cov.: 32 AF XY: 0.359 AC XY: 26710 AN XY: 74354

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.358

Alfa AF: 0.308 Hom.: 4097

Bravo AF: 0.379

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.27

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: rs582883; hg19: chr1-39835540;