Genetic Variant NM_203462.3:c.270C>A (chr4-6709360-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_203462.3(MRFAP1L1):c.270C>A(p.Asp90Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D90Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRFAP1L1
NM_203462.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.988

Publications

0 publications found

Variant links:

Genes affected

MRFAP1L1 (HGNC:28796): (Morf4 family associated protein 1 like 1) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

MRFAP1L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028214365).

BP6

Variant 4-6709360-G-T is Benign according to our data. Variant chr4-6709360-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3295844.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203462.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRFAP1L1	NM_203462.3	MANE Select	c.270C>A	p.Asp90Glu	missense	Exon 1 of 2	NP_982287.1	Q96HT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRFAP1L1	ENST00000320848.7	TSL:1 MANE Select	c.270C>A	p.Asp90Glu	missense	Exon 1 of 2	ENSP00000318154.6	Q96HT8
MRFAP1L1	ENST00000906128.1		c.270C>A	p.Asp90Glu	missense	Exon 1 of 2	ENSP00000576187.1
MRFAP1L1	ENST00000906129.1		c.270C>A	p.Asp90Glu	missense	Exon 1 of 2	ENSP00000576188.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.32

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0058

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.35

M_CAP

Benign

0.00097

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

-0.99

PrimateAI

Benign

0.45

PROVEAN

Benign

1.8

REVEL

Benign

0.026

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MutPred

0.23

Gain of glycosylation at S94 (P = 0.012)

MVP

0.040

MPC

0.27

ClinPred

0.054

GERP RS

-5.2

Varity_R

0.037

gMVP

0.011

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over