chr1-39084466-C-T

Variant names:

• chr1-39084466-C-T
• rs117942915
• ENST00000567887.5:c.220+28C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012090.5(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 NM_012090.5 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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 320 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_012090.5	c.220+28C>T		intron_variant	Intron 1 of 92		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000567887.5	c.220+28C>T		intron_variant	Intron 1 of 100	5		ENSP00000455823.1
MACF1	ENST00000372915.8	c.220+28C>T		intron_variant	Intron 1 of 95	5		ENSP00000362006.4
MACF1	ENST00000361689.7	c.220+28C>T		intron_variant	Intron 2 of 93	5		ENSP00000354573.2

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

GnomAD2 exomes AF: 0.00451 AC: 955 AN: 211590 AF XY: 0.00403

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 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 AC: 6 AN: 32938

Gnomad4 AMR exome AF: 0.000141 AC: 6 AN: 42538

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25796

Gnomad4 EAS exome AF: 0.0390 AC: 1509 AN: 38738

Gnomad4 SAS exome AF: 0.000829 AC: 70 AN: 84456

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 41386

Gnomad4 NFE exome AF: 0.0000773 AC: 85 AN: 1100040

Gnomad4 Remaining exome AF: 0.00411 AC: 245 AN: 59584

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 AC: 0.000385078 AN: 0.000385078

Gnomad4 AMR AF: 0.00124 AC: 0.00124167 AN: 0.00124167

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.0500 AC: 0.05 AN: 0.05

Gnomad4 SAS AF: 0.00124 AC: 0.00124327 AN: 0.00124327

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000191 AC: 0.000191143 AN: 0.000191143

Gnomad4 OTH AF: 0.00331 AC: 0.00331439 AN: 0.00331439

Alfa AF: 0.00100 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

May 21, 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	-0.90
CADD	Benign	0.42
DANN	Benign	0.61
Mutation Taster		=100/0	polymorphism

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;