chr7-1744893-C-T

Variant names:

• chr7-1744893-C-T
• rs202117598
• NM_001128636.4:c.297C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001128636.4(ELFN1):​c.297C>T​(p.Ile99Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,559,432 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (30 hom.)
• Consequence: ELFN1 NM_001128636.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.201
• Publications: 0 publications found

Genes affected

ELFN1 (HGNC:33154): (extracellular leucine rich repeat and fibronectin type III domain containing 1) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in synapse organization. Predicted to be located in dendrite and excitatory synapse. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 7-1744893-C-T is Benign according to our data. Variant chr7-1744893-C-T is described in ClinVar as Benign. ClinVar VariationId is 710659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.201 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128636.4. 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
	ELFN1	NM_001128636.4	MANE Select	c.297C>T	p.Ile99Ile	synonymous	Exon 4 of 4	NP_001122108.1	P0C7U0
	ELFN1	NM_001394187.1		c.297C>T	p.Ile99Ile	synonymous	Exon 3 of 3	NP_001381116.1	P0C7U0
	ELFN1	NM_001394188.1		c.297C>T	p.Ile99Ile	synonymous	Exon 4 of 4	NP_001381117.1	P0C7U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN1	ENST00000424383.5	TSL:5 MANE Select	c.297C>T	p.Ile99Ile	synonymous	Exon 4 of 4	ENSP00000456548.1	P0C7U0
	ELFN1	ENST00000561626.4	TSL:2	c.297C>T	p.Ile99Ile	synonymous	Exon 3 of 3	ENSP00000457193.1	P0C7U0
	ELFN1	ENST00000691883.1		c.297C>T	p.Ile99Ile	synonymous	Exon 3 of 3	ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152196 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00343 AC: 572 AN: 166762 AF XY: 0.00428

Gnomad AFR exome AF: 0.000429

Gnomad AMR exome AF: 0.000197

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.0000842

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00227 AC: 3188 AN: 1407118 Hom.: 30 Cov.: 31 AF XY: 0.00272 AC XY: 1893 AN XY: 694704

African (AFR) AF: 0.000250 AC: 8 AN: 32062

American (AMR) AF: 0.000329 AC: 12 AN: 36492

Ashkenazi Jewish (ASJ) AF: 0.00593 AC: 150 AN: 25316

East Asian (EAS) AF: 0.000299 AC: 11 AN: 36740

South Asian (SAS) AF: 0.0154 AC: 1231 AN: 79748

European-Finnish (FIN) AF: 0.00107 AC: 53 AN: 49542

Middle Eastern (MID) AF: 0.00596 AC: 34 AN: 5706

European-Non Finnish (NFE) AF: 0.00143 AC: 1545 AN: 1083134

Other (OTH) AF: 0.00247 AC: 144 AN: 58378

GnomAD4 genome AF: 0.00156 AC: 238 AN: 152314 Hom.: 2 Cov.: 33 AF XY: 0.00169 AC XY: 126 AN XY: 74476

African (AFR) AF: 0.000265 AC: 11 AN: 41572

American (AMR) AF: 0.000457 AC: 7 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0158 AC: 76 AN: 4816

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00171 AC: 116 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00191 Hom.: 0

Bravo AF: 0.00104

Asia WGS AF: 0.00779 AC: 29 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.4
DANN	Benign	0.84
PhyloP100		-0.20
Mutation Taster		=96/4	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: rs202117598; hg19: chr7-1784529; COSMIC: COSV106577336; COSMIC: COSV106577336;