4-6709609-G-C

Variant names:

• chr4-6709609-G-C
• rs763252388
• NM_203462.3:c.21C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203462.3(MRFAP1L1):​c.21C>G​(p.Asp7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MRFAP1L1 NM_203462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040833563).

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.21C>G	p.Asp7Glu	missense	Exon 1 of 2	NP_982287.1	Q96HT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRFAP1L1	ENST00000320848.7	TSL:1 MANE Select	c.21C>G	p.Asp7Glu	missense	Exon 1 of 2	ENSP00000318154.6	Q96HT8
	MRFAP1L1	ENST00000906128.1		c.21C>G	p.Asp7Glu	missense	Exon 1 of 2	ENSP00000576187.1
	MRFAP1L1	ENST00000906129.1		c.21C>G	p.Asp7Glu	missense	Exon 1 of 2	ENSP00000576188.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460832 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726458

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111084

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.6
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.53
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.015
Sift	Benign	0.61	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.12		Gain of helix (P = 0.0425)
MVP		0.14
MPC		0.29
ClinPred		0.052	T
GERP RS		-3.1
PromoterAI		0.0070	Neutral
Varity_R		0.049
gMVP		0.024
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs763252388; hg19: chr4-6711336;